C. O'Hear

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

G. Sellam

Employment or leadership position: F. Hoffmann‐La Roche Ltd

Stock ownership: F. Hoffmann‐La Roche Ltd

N. Horowitz

Employment or leadership position: Rambam Health Care Campus

Consultant or advisory role: F. Hoffmann‐La Roche Ltd

Honoraria: F. Hoffmann‐La Roche Ltd

Research funding: Takeda, Jonson

241 |ANTITUMORAL ACTIVITY OF THE NOVEL BTK

INHIBITOR TG‐1701 IS ASSOCIATED WITH DISRUPTION OF

IKAROS SIGNALING AND IMPROVEMENT OF ANTI‐CD20

THERAPY IN B‐CELL NON‐HODGKIN LYMPHOMA

M. L. Ribeiro

, D. Reyes‐Garau

, M. Vinyoles

, N. Proﬁtos‐Peleja

, J.

C. Santos

, M. Armengol

, M. Fernandez‐Serrano

, J. J. Bech‐Serra

P. Blecua

, E. Musulen

, C. De la Torre

, H. Miskin

, M. Esteller

, F.

Bosch

, P. Menendez

, E. Normant

, G. Roue

Josep Carreras Leukaemia Research Institute, Lymphoma Translational

group, Badalona, Spain,

TG Therapeutics, Inc, Preclinical Sciences, New

York, New York, USA,

Vall d'Hebron Institute of Oncology, Experimental

Hematology, Barcelona, Spain

Introduction: Covalent Bruton's tyrosine kinase inhibitors (BTKis)

have transformed the treatment of B‐cell non‐Hodgkin lymphoma (B‐

NHL). However, their activity has been often limited by 1) acquired

resistance due to the development of a cysteine to serine mutation at

the BTK catalytic site (BTKC481S) or over‐activation of the NF‐kB

pathway, and 2) off‐target activity that precluded their use in com-

bination with anti‐CD20 antibodies. TG‐1701 is a novel irreversible

and highly speciﬁc BTKi currently under study in patients with

relapsed/refractory (R/R) B‐NHL alone and in combination with

ublituximab, a new glycoengineered anti‐CD20 antibody, and

umbralisib, a dual PI3Kδand casein kinase‐1εinhibitor (also referred

to as the U2 regimen).

Methods: A set of 6 B‐NHL clinical samples from TG‐1701 phase 1 trial

were characterized by phosphoproteomic and RNA‐seq analysis, fol-

lowed by biomarker validations using real‐time PCR and western blot.

Activity of TG‐1701 either alone or in combination with U2 regimen

was evaluated by proliferation, antibody‐dependent cell cytotoxicity

(ADCC) and phagocytosis (ADCP) assays in a panel of n =10 B‐NHL co‐

cultures and in two mouse xenografts, including non‐canonical NFκB

and BTKC481S resistant models. Biomarker validation and signal

transduction analysis were conducted through immunoﬂuorescence,

immunohistochemical studies and gene knock‐out (KO) experiments.

Results: Phosphoproteomic analysis of tumoral lymphocytes from B‐

NHL patients receiving TG‐1701 led to a non‐supervised clustering

that matched the early clinical outcomes and separated a group of

early “responders” from a group of “non‐responders”. This clustering

was based on a selected list of 96 phosphosites, with Ikaros‐Ser442/

445 phosphorylation as a potential biomarker for TG‐1701 efﬁcacy.

RNA‐seq analysis revealed that TG‐1701 treatment blunted the

Ikaros gene signature, including YES1, MYC and IRF4, in responder

patients as well as in BTKi‐sensitive B‐NHL cell lines and xeno-

grafts. On the contrary, Ikaros nuclear activity and Ikaros‐

dependent gene regulation remained unaffected by the drug in

non‐responder patients and in BTKC481S , BTKKO and non‐

canonical NFκB models in vitro and in vivo. Interestingly, and in

contrast with the ﬁrst‐in‐class BTKI, ibrutinib, TG‐1701 did not

impair FcγR‐driven ADCC and ADCP triggered by the anti‐CD20

antibodies rituximab and ublituximab in different B‐NHL co‐

culture system, and cooperated with U2 in reducing the tumor

growth in both ibrutinib‐sensitive and ibrutinib‐insensitive mouse

models of B‐NHL.

Conclusions: Altogether, these data validate phosphoproteomic as a

valuable tool for the early detection of response to BTK inhibition in

the clinic, and for the determination of drug mechanism of action.

Our results also support the use of TG‐1701‐U2 combination in R/R

B‐NHL patients, irrespective of prior response to ibrutinib.

EA – previously submitted to regional or national meetings (up to

1000 attendees).

The research was funded by: TG Therapeutics, Fondo de Inves-

tigación Sanitaria PI18/01383, European Regional Development

Fund (ERDF) “Una manera de hacer Europa” (to GR).

Keywords: Molecular Targeted Therapies, Aggressive B‐cell

non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

G. Roue

Employment or leadership position: H. Miskin and E. Normant are

employees with stock ownership in TG Therapeutics, Inc

Research funding: G.Roué received research funding from TG

Therapeutics

242 |PROMISING CLINICAL DATA FROM DOSE ESCALATION

IN A PHASE IB/II ONGOING STUDY OF MOSUNETUZUMAB WITH

POLATUZUMAB VEDOTIN FOR RELAPSED/REFRACTORY B‐CELL

NON‐HODGKIN'S LYMPHOMA

C. Diefenbach

, E. Budde

, J. Chavez

, I. S. Lossos

, A. Mehta

, K.

Dorritie

, M. Kamdar

, R. Negricea

, S. Pham

, M. Hristopoulos

Ling‐Y. Huw

, C. O’Hear

, Y. Oki

, I. To

, N. Ghosh

Perlmutter Cancer Center at NYU Langone Health, Division of

Hematology and Medical Oncology, New York, USA,

City of Hope

National Medical Center, Hematology & Hematopoietic Cell

Transplantation, Duarte, California, USA,

Mofﬁtt Cancer Center,

Malignant Hematology, Tampa, USA,

Sylvester Comprehensive Cancer

Center, University of Miami Health System, Division of Hematology,

330

SUPPLEMENT ABSTRACTS

Miami, USA,

O’Neal Comprehensive Cancer Center at The University of

Alabama at Birmingham, Division of Hematology and Oncology,

Birmingham, USA,

UPMC Hillman Cancer Center, Division of

Hematology/Oncology, Pittsburgh, USA,

University of Colorado Cancer

Center, Medicine‐Hematology, Aurora, Colorado, USA,

F. Hoffmann‐La

Roche Ltd, Product Development ‐Clinical Safety, Basel, Switzerland,

Hoffmann‐La Roche Ltd, Product Development ‐Biometrics, Biostatistics,

Mississauga, Canada,

Genentech, Inc., In Vivo Pharmacology, South San

Francisco, USA,

Genentech, Inc., Department of Oncology Biomarker

Development, South San Francisco, USA,

Genentech, Inc., Product

Development Hematology, South San Francisco, USA,

Genentech, Inc.,

Product Development Oncology, South San Francisco, USA,

Genentech,

Inc., Product Development Clinical Science, South San Francisco, USA,

Levine Cancer Institute/Atrium Health, Hematologic Oncology and

Blood Disorders, Charlotte, USA

Introduction: Mosunetuzumab (M), a full‐length, humanized, IgG1

bispeciﬁc antibody targeting CD20 and CD3, has shown promising

efﬁcacy and safety as monotherapy for relapsed/refractory (R/R) B‐

cell non‐Hodgkin's lymphoma (B‐NHL; NCT02500407; Assouline,

et al. ASH 2020). The combination of M with the anti‐CD79b

antibody‐drug conjugate, polatuzumab vedotin (Pola), showed syn-

ergistic anti‐lymphoma activity in a mouse xenograft model. These

data supported a Phase Ib/II, open‐label, multicenter trial of M‐Pola

for R/R B‐NHL (GO40516, NCT03671018). Here we present early

clinical data from the Phase Ib cohort.

Methods: Patients (pts) with R/R follicular lymphoma (FL, grade [Gr]

1–3a) or aggressive NHL (aNHL), including de novo diffuse large B‐cell

lymphoma (DLBCL), transformed FL (trFL) and FL Gr 3b (FL3b),

received Cycle (C) 1 step‐up doses of M on Day (D) 1 (1mg) and D8

(2mg), the target dose on C1D15, then continued at the target dose

on C2D1 onwards. M was given every 21 days for eight cycles (or 17

cycles if stable disease or a partial response after C8). Pola (1.8mg/

kg) was given with M on D1 of each cycle for six cycles.

Results: As of November 17, 2020, 22 pts had received M‐Pola (M

target doses: 9mg, n =7; 20mg, n =3; 40mg, n =6; 60mg [with D1

dose of 30mg from C3 onwards], n =6). Pts had DLBCL (n =12), FL

(n =3), FL3b (n =3) and trFL (n =4). Pt characteristics include:

median age of 70 (38–81) years; median of 3 (1–10) prior lines of

therapy; 7 (32%) pts had prior CAR‐T therapy; 17 (77%) and 19 (86%)

pts had disease refractory to last prior therapy and prior anti‐CD20

therapy, respectively. Median follow‐up duration was 9.6 (0.7–23.7)

months. The most frequent treatment‐related adverse events (AEs)

were neutropenia (45.4%), fatigue, nausea and diarrhea (all 36.4%).

Cytokine release syndrome (CRS) was observed in 2 pts (9.1%; both

Gr 1 by ASTCT 2019 criteria). One dose‐limiting toxicity (Gr 3 new

onset atrial ﬁbrillation) was observed in the 40mg cohort. The

maximum tolerated dose was not exceeded. The most common Gr ≥3

and serious AEs were both neutropenia, observed in 8 (36.4%) and 3

(13.6%) pts, respectively. Two (9.3%) Gr 5 AEs occurred: sudden

cardiac death (n =1) and respiratory failure (n =1); neither was

deemed treatment related. No immune effector cell‐associated

neurotoxicity was observed. The Table shows preliminary efﬁcacy

data.

Conclusions: These data indicate that M‐Pola has an acceptable

safety proﬁle, with no Gr ≥2 CRS observed, and promising efﬁcacy in

pts with R/R NHL with predominantly aggressive disease. The Phase

II expansion cohort in R/R DLBCL is ongoing, with no mandatory

hospitalization required.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: F. Hoffmann‐La Roche Ltd. Third‐party

medical writing assistance, under the direction of the authors, was

provided by Katie Buxton and Khalida Rizi of Ashﬁeld MedComms, an

Ashﬁeld Health company, and was funded by F. Hoffmann‐La Roche

Ltd.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Immunotherapy

Conﬂicts of interests pertinent to the abstract

C. Diefenbach

Consultant or advisory role: Seattle Genetics, Bayer, Bristol‐Myers

Squibb, F. Hoffmann‐La Roche Ltd/Genentech, Inc., Merck, Janssen,

Celgene, MorphoSys

Stock ownership: Gilead Sciences

Research funding: Seattle Genetics, Genentech, Inc., Incyte, LAM

Therapeutics, Merck, Bristol‐Myers Squibb, Millennium, F. Hoffmann‐

La Roche Ltd/Genentech, Inc., Janssen, MEI Pharma, Trillium

Therapeutics

E. Budde

Consultant or advisory role: F. Hoffmann‐La Roche Ltd/Genentech,

Inc., Kite/Gilead, Novartis

Honoraria: AstraZeneca

Research funding: Merck, Amgen, MustangBio, AstraZeneca

TABLE: Preliminary efﬁcacy in the dose‐escalation cohort

SUPPLEMENT ABSTRACTS

331

Educational grants: F. Hoffmann‐La Roche Ltd/Genentech, Inc., Kite/

Gilead, AstraZeneca

Other remuneration: Speakers' bureau: Kite, AstraZeneca; Patents,

royalties, other intellectual property: patents pending

J. Chavez

Consultant or advisory role: Kite/Gilead, Bayer, Novartis, Kar-

yopharm Therapeutics, Verastem, Pﬁzer, MorphoSys, TeneoBio, Juno

Therapeutics, Celgene

Research funding: Merck

Other remuneration: Speakers' Bureau: Kite/Gilead, Genentech, Inc.,

AstraZeneca, BeiGene

I. S. Lossos

Consultant or advisory role: Seattle Genetics, Janssen Scientiﬁc Af-

fairs, Verastem

Honoraria: Janssen Biotech

Research funding: National Cancer Institute

Other remuneration: Royalties: Stanford

A. Mehta

Consultant or advisory role: Spectrum Pharmaceuticals, Aileron

Therapeutics, Bristol‐Myers Squibb, Seattle Genetics, Kite, Pharma-

cyclics, TG Therapeutics, Incyte, Kyowa Kirin International, Rigel

Research funding: Incyte, F. Hoffmann‐La Roche Ltd/Genentech, Inc.,

Merck, Bristol‐Myers Squibb, Juno Therapeutics, Gilead Sciences,

Forty Seven, Takeda, Astex Pharmaceuticals, Pharmacyclics/Janssen,

Epizyme, Aileron Therapeutics, Oncotartis, ADC Therapeutics, Seat-

tle Genetics, Innate Pharma, TG Therapeutics, Afﬁrmed Therapeutics,

ADC Therapeutics, Rhizen Pharmaceuticals

Other remuneration: Speakers' bureau: Spectrum Pharmaceuticals,

Kite, Gilead Sciences, Seattle Genetics, Incyte

K. Dorritie

Honoraria: OncLive

Research funding: Kite, F. Hoffmann‐La Roche Ltd/Genentech, Inc.,

Juno Therapeutics, Nordic Nanovector, Genmab/Seattle Genetics,

Janssen Research & Development

Educational grants: Kite, Nordic Nanovector

M. Kamdar

Consultant or advisory role: AstraZeneca, Celgene, Pharmacyclics/

Janssen, Adaptive Biotechnologies, Karyopharm Therapeutics, Abb-

Vie, BeiGene

Research funding: TG Therapeutics

Other remuneration: Speakers' Bureau: Seattle Genetics

R. Negricea

Employment or leadership position: F. Hoffmann‐La Roche Ltd

S. Pham

Employment or leadership position: Roche Institute for Clinical

Evaluative Sciences

M. Hristopoulos

Employment or leadership position: Genentech, Inc.

Stock ownership: Genentech, Inc.

Ling‐Y. Huw

Employment or leadership position: Genentech, Inc.

Stock ownership: Genentech, Inc.

Educational grants: Genentech, Inc.

C. O’Hear

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

Y. Oki

Employment or leadership position: Genentech, Inc.; Immediate

family member: Jazz Pharmaceuticals

I. To

Employment or leadership position: Genentech, Inc.

Educational grants: Genentech, Inc.

N. Ghosh

Consultant or advisory role: Seattle Genetics, TG Therapeutics,

AstraZeneca, Verastem, Pharmacyclics/Janssen, Karyopharm Thera-

peutics, Genmab, Bristol‐Myers Squibb, Gilead Sciences, Adaptive

Biotechnologies, BeiGene

Research funding: Pharmacyclics, TG Therapeutics, F. Hoffmann‐La

Roche Ltd/Genentech, Inc., Seattle Genetics, Juno Therapeutics,

Forty Seven

Other remuneration: Speakers' bureau: AbbVie, Janssen Oncology,

Kite/Gilead, Seattle Genetics, AstraZeneca, Bristol‐Myers Squibb,

Celgene, Pharmacyclics/Janssen, Epizyme

243 |POLATUZUMAB VEDOTIN +RITUXIMAB +

LENALIDOMIDE IN PATIENTS (PTS) WITH RELAPSED/

REFRACTORY (R/R) DIFFUSE LARGE B‐CELL LYMPHOMA

(DLBCL): PRIMARY ANALYSIS OF A PHASE 1B/2 TRIAL

C. Diefenbach

, P. Abrisqueta

, E. Gonzalez‐Barca

, C. Panizo

, J.

Maria Arguinano Perez

, F. Miall

, M. Bastos‐Oreiro

, A. Lopez‐

Guillermo

, L. Banerjee

, A. McMillan

, J. Hirata

, L. Musick

, S.

Saha

, B. Croft

, E. Seymour

Perlmutter Cancer Center at NYU Langone Health, New York, New York,

USA,

Hospital Vall Hebron, Department of Haematology, Barcelona,

Spain,

Instititut Catala D'Oncologia, IDIBELL, Universitat de Barcelona,

Barcelona, Spain,

Clínica Universidad de Navarra, IdiSNA, Servicio de

Hematología, Pamplona, Spain,

Complejo Hospitalario de Navarra,

Department of Haematology, Pamplona, Spain,

University Hospitals of

Leicester NHS Trust, Department of Haematology, Leicester, UK,

Hospital

General Universitario Gregorio Marañón, Department of Haematology,

Madrid, Spain,

Hospital Clínic de Barcelona, Department of

Haematology, Barcelona, Spain,

Maidstone and Tunbridge Wells NHS

Trust, Oncology Centre, Kent, UK,

Nottingham University Hospitals NHS

Trust, Centre for Clinical Haematology, Nottingham, UK,

Genentech,

Inc., Product Development Oncology, South San Francisco, USA,

Hoffmann‐La Roche Ltd, Product Development Biometrics, Welwyn Gar-

den City, UK,

Karmanos Cancer Institute/Wayne State University,

Department of Oncology, Detroit, USA

332

SUPPLEMENT ABSTRACTS

Introduction: The combination of polatuzumab (Pola) +rituximab

(R) +lenalidomide (Len) may enhance anti‐tumor response in R/R

DLBCL. Here, we report the primary analysis of the R/R DLBCL

cohort in a Phase 1b/2 study (GO29834; NCT02600897).

Methods: Pts received induction with 6 x 28‐Day (D) cycles (C) of:

Pola 1.8mg/kg intravenous (IV; C1−6: D1); R 375mg/m

IV (C1−6:

D1) and oral Len 10–20mg (dose escalation) or recommended Phase

2 dose (RP2D) daily on D1–21. Pts with a response at end of in-

duction (EOI) received 6 months (mo) consolidation with R 375mg/

(D1 every 2 mo) and Len 10mg (D1–21 monthly). Primary end-

points were safety/tolerability and positron emission tomography

(PET)‐complete response (CR) rate at EOI by independent review

committee (IRC) by modiﬁed Lugano criteria.

Results: At primary analysis (Sep 08, 2020), 57 pts were enrolled.

Median age was 71 years (range 28–92); male (67%); Ann Arbor

Stage III–IV (86%); International Prognostic Index 3–5 (60%); me-

dian 2 prior therapies; prior bone marrow transplant (11%); prior

CAR‐T therapy (5%); primary refractory (49%) and refractory to last

therapy (65%). Grade 3–4 adverse events (AEs) were experienced

by 75% of pts, most commonly, neutropenia (58%), thrombocyto-

penia (14%), infections (14%) and anemia (11%). AEs led to Len dose

reduction in 25% and interruption in 63% of pts. One Grade 5

treatment‐related AE (neutropenic sepsis) was reported. In total, 49

pts were treated at RP2D (Pola 1.8mg/kg +Len 20mg). IRC PET‐CR

rate at EOI was 29% (Table). A best overall response (BOR)

assessed by investigator (INV) was seen in 36/49 (74%) pts with 17/

49 (35%) pts achieving a CR; of these, 14/17 (82%) remain in

remission at the cutoff date. Median duration of response (DOR)

was 8.1 mo (95% conﬁdence interval [CI]: 4.7–not evaluable [NE]).

After a median follow‐up of 9.7 mo, median progression‐free

survival (PFS) and overall survival (OS) were 6.3 mo (95% CI: 4.5–

9.7) and 10.9 mo (95% CI: 7.4–NE), respectively.

Conclusions: Our study of the novel triplet combination, Pola‐R‐Len,

demonstrates a tolerable safety proﬁle. This ﬁrst efﬁcacy report of

Pola‐R‐Len shows promising activity in a difﬁcult‐to‐treat R/R

DLBCL population, particularly in pts achieving CR, a large propor-

tion of whom remain in remission at the cutoff date. Further eval-

uation of Pola‐R‐Len and the impact of consolidation therapy is

warranted to address the signiﬁcant unmet need in this patient

population.

EA – previously submitted to ASCO 2021.

The research was funded by: F. Hoffmann‐La Roche Ltd/Genentech,

Inc. Third‐party editorial assistance, under the direction of the au-

thors, was provided by Angela Rogers, PhD, of Ashﬁeld MedComms,

an Ashﬁeld Health company, and was funded by F. Hoffmann‐La

Roche Ltd.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Molecular

Targeted Therapies Combination, Therapies

Conﬂicts of interests pertinent to the abstract

C. Diefenbach

Consultant or advisory role: Seattle Genetics, Bayer, Bristol‐Myers

Squibb, Genentech, Inc./F. Hoffmann‐La Roche Ltd, Merck, Janssen,

Celgene, MorphoSys

Stock ownership: Gilead Sciences

Research funding: Seattle Genetics, Genentech, Inc., Incyte, LAM

Therapeutics, Merck, Bristol‐Myers Squibb, Millennium, F. Hoffmann‐

La Roche Ltd/Genentech, Inc., Janssen, MEI Pharma, Trillium

Therapeutics

SUPPLEMENT ABSTRACTS

333

P. Abrisqueta

Consultant or advisory role: Janssen, F. Hoffmann‐La Roche Ltd,

Astrazeneca, Celgene, Abbvie

Honoraria: Janssen, F. Hoffmann‐La Roche Ltd, Astrazeneca, Cel-

gene, Abbvie, Gilead

E. Gonzalez‐Barca

Consultant or advisory role: Janssen, AbbVie, Celgene, Gilead, Kiowa,

Eusapharma

Educational grants: Janssen, AbbVie, Takeda

Other remuneration: Speakers' bureau: Janssen, AbbVie, Takeda

C. Panizo

Consultant or advisory role: Roche Pharma

Educational grants: Roche Pharma

Other remuneration: Speakers' bureau: Janssen, Roche Pharma;

Expert testimony: Celgene, Incyte

J. Maria Arguinano Perez

Honoraria: Janssen, Takeda, F. Hoffmann‐La Roche Ltd, Celgene,

Novartis, Amgen

Educational grants: Amgen, Celgene, Janssen

Other remuneration: Speakers' bureau: Celgene, Janssen, Amgene

F. Miall

Consultant or advisory role: F. Hoffmann‐La Roche Ltd, Takeda

Honoraria: F. Hoffmann‐La Roche Ltd, Takeda

Educational grants: F. Hoffmann‐La Roche Ltd, Takeda

M. Bastos‐Oreiro

Consultant or advisory role: Kite, Celgene, F. Hoffmann‐La Roche Ltd

Research funding: F. Hoffmann‐La Roche Ltd

Educational grants: Kite, F. Hoffmann‐La Roche Ltd, Celgene, Takeda

Other remuneration: Speakers' bureau: F. Hoffmann‐La Roche Ltd,

Kite, Celgene, Takeda

A. Lopez‐Guillermo

Consultant or advisory role: F. Hoffmann‐La Roche Ltd, Gilead/Kite,

Celgene, Incyte, Janssen

Research funding: F. Hoffmann‐La Roche Ltd, Gilead, Celgene

L. Banerjee

Educational grants: Gilead, Takeda, Novartis

A. McMillan

Consultant or advisory role: F. Hoffmann‐La Roche Ltd, AbbVie

Honoraria: F. Hoffmann‐La Roche Ltd, AbbVie

Educational grants: F. Hoffmann‐La Roche Ltd, Celgene/Bristol‐

Myers Squibb

Other remuneration: Speakers' bureau: F. Hoffmann‐La

Roche Ltd

J. Hirata

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

L. Musick

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd/GNE

S. Saha

Employment or leadership position: Genentech, Inc.

B. Croft

Employment or leadership position: Genentech, Inc.

Stock ownership: Genentech, Inc,/F. Hoffmann‐La Roche Ltd

E. Seymour

Employment or leadership position: Flatiron Health

Consultant or advisory role: Karyopharm, Janssen Oncology, Garner

Health

Stock ownership: F. Hoffmann‐La Roche Ltd

Research funding: Karyopharm

244 |SAFETY AND EFFICACY OF CD37‐TARGETING

NARATUXIMAB EMTANSINE PLUS RITUXIMAB IN DIFFUSE

LARGE B‐CELL LYMPHOMA AND OTHER NON‐HODGKIN'S B‐

CELL LYMPHOMAS – A PHASE 2 STUDY

M. Y. Levy

, Z. Grudeva‐Popova

, M. Trneny

, W. Jurczak

, H. Pyly-

penko

, D. Jagadeesh

, M. Andre

, S. Nasta

, D. Rechavi‐Robinson

, S.

Toffanin

, S. Micallef

, A. Attinger

, E. Rouits

, M. Dymkowska

, H.

Nauwelaerts

, F. J. S. H. Woei‐A‐Jin

Texas Oncology‐Baylor Charles A. Sammons Cancer Center, Dallas, TX,

USA, Department of Hematology, Medical Oncology, Dallas, USA,

Med-

ical University of Plovdiv, Department of Clinical Oncology, Plovdiv,

Bulgaria,

General Hospital, Charles University, Prague, Czech Republic,

Maria Sklodowska‐Curie National Research Institute of Oncology,

Department of Clinical Oncology, Krakow, Poland,

Cherkassy Regional

Oncological Center, Department of Hematology, Cherkassy, Ukraine,

Cleveland Clinic, Department of Hematologic Oncology and Blood Dis-

orders, Cleveland, USA,

UCL Namur, Centre Hospitalier Universitaire

Dinant Godinne, Yvoir, Belgium,

Perelman School of Medicine, University

of Pennsylvania, Division of Hematology/Oncology, Philadelphia, USA,

Debiopharm International S.A., Clinical Development, Lausanne,

Switzerland,

University Hospitals Leuven, Department of General

Medical Oncology, Leuven, Belgium

Introduction: Naratuximab emtansine (nara, Debio 1562, formerly

IMGN529) is an antibody‐drug conjugate consisting of a humanized

anti‐CD37 antibody, K7153A, conjugated via a thioether‐based

linker to a cytotoxic maytansinoid, DM1. CD37, a lymphocyte sur-

face marker, is highly expressed in B‐cell non‐Hodgkin lymphoma (B‐

NHL), including diffuse large B‐cell lymphoma (DLBCL). In preclinical

models of B‐NHL, nara demonstrated strong antitumor activity,

further enhanced by co‐administration of rituximab (RTX). A Phase 1

monotherapy study of nara revealed a good safety proﬁle and

promising efﬁcacy (22% overall response rate [ORR] in DLBCL at all

doses). Here we report results from an open label Phase 2 study to

334

SUPPLEMENT ABSTRACTS

evaluate the safety and efﬁcacy of nara in combination with RTX in

patients (pts) with relapsed and/or refractory (R/R) DLBCL and other

forms of B‐NHL.

Methods: R/R B‐NHL pts with 1‐6 prior lines of treatment were

recruited to two study parts. In Part 1, which included a safety run‐in,

pts received 0.7 mg/kg nara in combination with 375 mg/m

RTX

every 3 weeks (Q3W). In Part 2, only R/R DLBCL pts were included.

Pts were assigned to either the Q3W regimen, or to a weekly

regimen of 0.4, 0.2, and 0.2 mg/kg nara administered on days 1, 8, and

15, respectively, combined with 375 mg/m

RTX on day 1. Treatment

was administered for 6 cycles with possible extension. Primary

endpoints were treatment emergent adverse events (TEAEs) and

ORR. Safety is reported in all pts; efﬁcacy only in DLBCL pts. Data

cut‐off was 30‐Sep‐2020, when the trial was still ongoing; ﬁnal data

from the end of study will be available in the full presentation (FP)

(NCT02564744).

Results: 100 pts were enrolled in the study: 80 DLBCL and 20 other

B‐NHL pts, of whom 82 (82%) experienced grade ≥3 TEAEs, the most

common being neutropenia 54 (54%), lymphopenia 17 (17%) and

thrombocytopenia 11 (11%). Only 10 (10%) pts discontinued nara

due to a TEAE. Only very few grade ≥3 TEAEs, known to be asso-

ciated with free DM1, were reported: 1 (1%) serious AE of toxic

hepatitis with no sequelae; and 2 (2%) cases of non‐serious neurop-

athy (1 motor and 1 sensory). At the time of data cutoff, of the 80

DLBCL pts, 74 (32% refractory to 1

and/or last line) were efﬁcacy

evaluable (had one screening assessment and at least one post‐

baseline tumor assessment or clinical progressive disease [PD]).

The ORR was 43.2%, with 24 (32.4%) complete responses and 8

(10.8%) partial responses. In addition, 11 (14.9%) stable disease and

31 (41.9%) PD were observed. Median duration of response was not

reached, (95% conﬁdence interval 10.4 ‐NA months [mo]). Median

duration of follow‐up in responders was 13.7 mo.

Conclusions: The combination of nara with RTX was well tolerated,

with a manageable safety proﬁle of expected, mainly hematological

AEs. A preliminary analysis shows promising efﬁcacy. Final data,

regimen comparison, and related analyses will be available in the FP.

The research was funded by: Debiopharm International S.A.

Keywords: Molecular Targeted Therapies, Aggressive B‐cell non‐

Hodgkin lymphoma, Combination Therapies

Conﬂicts of interests pertinent to the abstract

M. Trneny

Consultant or advisory role: Celgene, Janssen, Gilead, Bristol‐Meyers

Squibb, Amgen, Abbvie, Takeda, F. Hoffmann‐La Roche Ltd, Mor-

phoSys, Incyte

Honoraria: Janssen, Gilead, Bristol‐Meyers Squibb, Amgen, Abbvie,

Takeda, F. Hoffmann‐La Roche Ltd, MorphoSys, Incyte

Educational grants: Abbvie, Gilead, Bristol‐Meyers Squibb, Takeda, F.

Hoffmann‐La Roche Ltd., Janssen

W. Jurczak

Consultant or advisory role: Mei pharma, Debiopharm, Loxo, Takeda,

Acerta, Astra Zeneca, Beigene

Research funding: GSK, Acerta, Astra Zeneca, Bayer, Beigene, Nordic

Nanovector, Incyte, Debiopharm, Genenthech, Janssen, Loxo, Mei

Pharma, Morphosys, Takeda, TG Therapeutics, Gilead

S. Nasta

Consultant or advisory role: Merck (DSMB)

Honoraria: Morphosys (Advisory Board)

Research funding: Debiopharm, ATARA, Roche, Rafael, Takeda/Mil-

lenium, Pharmacyclics

D. Rechavi‐Robinson

Employment or leadership position: Employed by Debiopharm In-

ternational S.A.

S. Toffanin

Employment or leadership position: Employed by Debiopharm In-

ternational S.A.

S. Micallef

Employment or leadership position: Debiopharm International ‐R&D;

Biostatistics & Data Management ‐Biostatistics Program Lead

A. Attinger

Employment or leadership position: Debiopharm International S.A.

E. Rouits

Employment or leadership position: Debiopharm International S.A.

M. Dymkowska

Consultant or advisory role: Debiopharm International S.A., Argenx

BV, MorphoSys AG, Aurealis OY

H. Nauwelaerts

Employment or leadership position: Debiopharm International S.A.

245 |PROSPECTIVE EVALUATION OF LYMPHOMA RESPONSE

TO IMMUNOMODULATORY THERAPY CRITERIA (LYRIC) IN

GATA TRIAL FROM THE LYSA GROUP

Y. Al Tabaa

, O. Casasnovas

, C. Baillet

, E. Bachy

, E. Nicolas

Virelizier

, J. M. Schiano de Colella

, C. Bailly

, S. Kanoun

S. Guidez

, E. Gyan

, R. Gressin

, N. Morineau

, L. Ysebaert

S. Le Gouill

, H. Tilly

, R. Houot

, F. Morschhauser

G. Cartron

, C. Herbaux

Scintidoc, Nuclear Medicine Center, Montpellier, France,

CHU

François Mitterrand, Hematology, Dijon, France,

CHU Lille, Nuclear

Medicine, Lille, France,

CHU Lyon, Hematology, Lyon, France,

CRLC

Lyon, Hematology, Lyon, France,

Institut Paoli‐Calmettes, Hematology,

Marseille, France,

CHU Nantes, Nuclear Medicine, Nantes, France,

Oncopole Toulouse, Nuclear Medicine, Toulouse, France,

CHU Poit-

iers, Hematology, Poitiers, France,

CHU Tours, Hematology,

Tours, France,

CHU Grenoble, Hematology, Grenoble, France,

CHD

Vendée, Hematology, La Roche sur Yon, France,

Oncopole Tou-

louse, Hematology, Toulouse, France,

CHU Nantes, Hematology,

SUPPLEMENT ABSTRACTS

335

Nantes, France,

Centre Henri Becquerel, Hematology, Rouen,

France,

CHU Rennes, Hematology, Rennes, France,

CHU Lille,

Hematology, Lille, France,

CHU Montpellier, Hematology, Montpellier,

France

Introduction: Checkpoint blockade may complicate response

assessment by a ﬂare reaction or pseudoprogression (PP). To avoid

the mistake of considering a new agent ineffective, it was pro-

posed to add the category “indeterminate response” (IR) to Lugano

classiﬁcation, in the LYmphoma Response to Immunomodulatory

Therapy Criteria (LYRIC): 1/ increase in overall tumor burden in

the ﬁrst 12 weeks of therapy, without clinical deterioration

(IR1), 2/ development of new lesions without overall progression

(IR2), or 3/ increased FDG avidity despite no change in lesion

size (IR3). These patterns are deﬁned as progressive metabolic

disease (PMD) in the Lugano criteria. A PP was deﬁned as an IR

that became a partial or complete metabolic response (PMR or

CMR) at next evaluation. The aim of this study is to assess in a

practical and prospective manner the LYRIC criteria in relapsed/

refractory (R/R) DLBCL and FL treated with atezolizumab, ven-

etoclax and obinutuzumab (GATA trial), and measuring the inci-

dence of PP.

Methods: The GATA study is a LYSA sponsored multicenter

phase 2 trial (NCT03276468) evaluating the combination of

atezolizumab, obinutuzumab and venetoclax in biopsy‐conﬁrmed

R/R DLBCL and FL patients who failed at least one line of ther-

apy (rituximab and anthracycline containing regimen). Local im-

aging practitioners used the Lugano and LYRIC classiﬁcation.

Clinical investigators were warned of the possibility of PP, and

a coordinating investigator's approval was required before

stopping treatment. A centralized imaging review on PET‐CT scan

was performed at three time points: baseline, cycle 4 (C4, 12

weeks) and cycle 8 (C8, 24 weeks), on Lugano and LYRIC

criteria.

Results: Our study has included 116 patients (58 DLBCL, 58 FL)

from GATA trial. The overall metabolic response rate at C8 was

23.6% and 53.6% with a median follow up of 9 months and 14.5

months for DLBCL and FL patients, respectively. Ninety‐ﬁve pa-

tients had a centralized review at C4 and 57 at C8. Missing pa-

tients are those who progressed prior to the restaging by PET‐CT

scan. In Lugano criteria, 84 reviewed responses (88.4%) were

concordant with local response at C4, and 47 (82.5%) at C8. In

LYRIC criteria, 9 patients (4 DLBCL and 5 FL) were classiﬁed at C4

as IR by both local reading and centralized review, with a

discordance in the type of IR (1, 2 or 3) in 6/9 cases. During the

follow‐up, 4 cases turned out to be PP (1 DLBCL and 3 FL) and 5

cases real progressive diseases (PD). One PP is illustrated in Figure

1 (IR3 at C4, CMR at C8). At C8, 7 patients were classiﬁed as IR

by centralized review (IR2 and IR3), only 2 of them were IR by

local reading. During the follow‐up, all of those cases turned out to

be real PD within 1 to 3 cycles of therapy.

Conclusions: We observed a low frequency of 3.4% of PP at C4.

Interestingly, all IRs at C8 were found to be real PD. Overall, these

data are in favor of using the LYRIC classiﬁcation, but only for early

evaluation.

EA – previously submitted to EHA 2021.

Keywords: PET‐CT, Aggressive B‐cell non‐Hodgkin lymphoma,

Indolent non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

ONGOING TRIALS

246 |RADIATION FREE THERAPY OR THE INITIAL

TREATMENT OF GOOD PROGNOSIS EARLY NON‐BULKY

HODGKIN LYMPHOMA, DEFINED BY A LOW METABOLIC

TUMOR VOLUME AND A NEGATIVE PET‐2‐RAFTING TRIAL

A. Gallamini

, J. Walewski

, A. Rambaldi

, S. Viviani

, A. Sureda

, M.

André

, C. Rossi

, A. Moccia

, E. Zucca

, D. Rossi

, A. Filippi

, M.

Meignan

, S. Chauvie

, J. M. Zaucha

Antoine Lacassagne Cancer Center, Research and Clinical Innovation, Nice,

France,

Marii Skłodowskiej‐Curie Institute, Onco‐Hematology, Warsaw,

Poland,

Ospedale Papa Giovanni XXIII, Hematology, Bergamo, Italy,

Istituto Europeo di Ematologia, Hematology, Milano, Italy,

Institut Català

d'Oncologia, Hematology, Barcelona, Spain,

Cliniques universitaires Saint‐

Luc ‐UC Louvain, Hematology, Louvain, Belgium,

CHU Bocage, Hematol-

ogy, Dijon, France,

Istituto Oncologico della Svizzera Italiana, Hematology,

Bellinzona, Switzerland,

Policlinico S. Matteo, IRCCS, Radiation Oncology,

Pavia, Italy,

Henry Mondor Hospital, LYSA Imaging, Paris, France,

Ospedale S. Croce e Carle, Medical Physics, Cuneo, Italy,

Medical Uni-

versity of Gdansk, Hematology, Gdansk, Poland

Introduction: Early‐stage Hodgkin Lymphoma (eHL) is a curable

disease with a 5‐Y PFS and OS >85‐95% and 95%, respectively, after

combined modality treatment (CMT) with 2‐4 cycles of chemo-

therapy (CT) followed by 20 or 30 Gy Involved‐node radiotherapy

(RT). However, the efﬁcacy of CMT is offset by a long‐term morbidity,

with a cumulative incidence of Second Primary Malignancy (SPM) at

336

SUPPLEMENT ABSTRACTS

40 years of 48.5%, and a standardized incidence ratio 4.6 folds higher

than the age‐matched control population, with SPMs arising mostly

in areas included in RT ﬁelds (Schaapveld 2015). The RAFTING trial is

aimed to answer a still unmet need: is possible to deliver a RT‐free

treatment in most patients (p.) with good‐prognosis (no bulky, B

symptoms or extranodal) eHL (gp‐eHL), with a similar efﬁcacy to

CMT? The RAFTING trial is expected to answer these questions: (1)

Main endpoint: could the majority of good‐prognosis early cHL (gpe‐

cHL) be treated with 4 ABVD cycles with a 3‐Y PFS ≧90% with a

risk‐and response‐adapted strategy? Secondary endpoints: (2) Could

we deliver RT “on demand” in gpe‐cHL in “limited” relapse after CT

followed by Nivolumab maintenance (Nivo‐m), with an acceptable

overall effectiveness? (3) Could we increase the effectiveness of CMT

in PET‐2 positive eHL by adding one‐year Nivo‐m? (4) Could we

anticipate the diagnosis of an impending relapse during follow‐up of

p. in CR after chemo alone by cell‐free DNA monitoring?

Methods: In the RAFTING trial, a phase 2, multicenter, prospective

study sponsored by the Gdansk (PL) University, 160 nonbulky stage

I‐IIA HL p. will be enrolled in 5 European countries with an accrual

time of 18 months and a minimum follow‐up of 36 months. For

treatment planning p. will be stratiﬁed into three risk categories

according to (a) modiﬁed EORTC criteria (m‐EORTC), (b) interim PET

after 2 ABVD (PET‐2) and (3) Metabolic Tumor Volume (MTV)

computed in baseline PET. In the mEORTC criteria bulky and B‐

symptoms were taken over by a “Large Nodal Mass”, with the

largest diameter ≥5 cm., which proved a poor response predictor in

stage I‐IIA, PET‐2 negative HL p. treated with chemo alone (IIlidge

2020). P. stratiﬁcation: (1): P. with a negative PET‐2 and a low MTV

(P. group 1: 80%), will be treated with 2 or 4 ABVD cycles according

to their mEORTC risk and upon CR entry, they will be addressed to a

stringent clinical follow‐up every 3 months, and cfDNA assay every 6

months for the ﬁrst 18 months. (2) Low MTV and negative PET‐2 p.

failing ﬁrst‐line treatment with CT alone (P. group 2: 10%). As a

“limited relapse” (stage I ‐II) is expected to occur in 60‐70% of cases

(André 2017, Bröckelman 2021), these p. will be treated with INRT

“on demand” at the dose of 36 Gy, followed by Nivo‐m. (3): P. with a

positive PET‐2, whatever their MTV, or p. with a negative PET‐2 and

a high MTV (P. group 3: 10%). will be treated with 2 more ABVD

followed by INRT, 20 or 30 Gy, depending on the risk class according

to mEORTC criteria, and Nivo‐m.

The research was funded by: he research was funded by the Polish

Medical Research Agency

Keywords: Ongoing Trials

No conﬂicts of interests pertinent to the abstract.

247 |ANIMATE: A PHASE II STUDY OF NIVOLUMAB IN

TRANSPLANT ELIGIBLE PATIENTS WITH RELAPSED/

REFRACTORY CLASSIC HODGKIN LYMPHOMA

S. Booth

, A. Kirkwood

, P. Johnson

, S. Barrington

, E. Gallop‐

Evans

, K. Peggs

, V. Warbey

, C. Burton

, A. Ardavan

, B. Phillips

, E.

Lawrie

, L. Pike

, M. Northend

, L. Clifton‐Hadley

, R. Jenner

, G.

P. Collins

SUPPLEMENT ABSTRACTS

337

Oxford University Hospitals, Department of Haematology, Oxford, UK,

UCL Cancer Institute, CR UK and UCL Cancer Trials Centre, London, UK,

University of Southampton, Department of Medicine, London, UK,

King's

College London, King's College London and Guys’ & St Thomas PET

Imaging Centre, London, UK,

Velindre University NHS Trust, Department

of Oncology, Cardiff, UK,

University College London Hospitals,

Haematology, London, UK,

Leeds Cancer Centre, Haematology, Leeds,

UK,

University of Oxford, Department of Physics, Oxford, UK,

University

of Manchester and Manchester Academic Health Science Centre, Division

of Cancer Science, Manchester, UK,

UCL Cancer Institute, CR UK and

UCL Cancer Trials Centre, London, UK

Background: Relapsed or refractory (R/R) classic Hodgkin lymphoma

(cHL) has a poor outlook with chemotherapy alone (long‐term sur-

vival 10‐20%). In ﬁt patients, non cross‐reacting salvage regimens

and high dose chemotherapy with autologous stem cell transplant

(ASCT) improve 5 year freedom from second failure (FF2F) to 42%.

Progressive disease, toxicity of salvage therapy and failure to harvest

stem cells are common barriers to ASCT. The most discriminating

reported prognostic factor for ASCT outcome is pre‐transplant

response by PET (3‐5 year PFS >70% if PET negative; 25‐30% if

PET positive).

Programmed cell death protein 1 (PD‐1) inhibitors have estab-

lished efﬁcacy in R/R cHL, with overall response rates (ORR) of 69‐

72% and complete metabolic response rates (CMR) of 16‐37%. PD‐1

inhibitors warrant exploration as salvage therapy because ORR ap-

pears to be at least as good as with cytotoxic chemotherapy or

brentuximab vedotin, they are not typically myelosuppressive, help-

ing preserve ﬁtness, and responses are relatively durable allowing

time for transplant.

PD‐1 expression by immunohistochemistry (IHC) and 9p24 copy

gain by FISH are reported to correlate with response to PD‐1 in-

hibitors. Serial serum TARC (thymus and activation‐regulated che-

mokine) is reported to be prognostic in the frontline treatment of

cHL and may aid response assessment.

Methods: ANIMATE is a Phase II single‐arm multicentre study in the

UK assessing the safety and efﬁcacy of 4‐8 doses of nivolumab 240

mg every 14 days as second or third line therapy for R/R cHL in

ASCT‐ﬁt patients. Eligible patients must be ≥16 years, and about to

receive or be receiving ﬁrst or second line therapy (£ 14 days after

FIGURE 1 ANIMATE trial schema. PET CT Positorn emission tomography with contrast enhanced computed tomography *indeterminate

Response modiﬁed form Lymphoma Response to immunomodulatory Therapy Criteria of Cheson et al., 2016

338

SUPPLEMENT ABSTRACTS

last treatment in cycle 2 (cycle 3 or 4 if receiving brentuximab

vedotin)). Patients with autoimmune disorders, colitis, inﬂammatory

bowel disorders or pneumonitis are excluded. Trial treatment eligi-

bility, assessments and patient progress are shown in Fig 1.

The primary endpoint is ORR by PET after 4‐8 cycles of nivolu-

mab. The study is powered to exclude an ORR <40% for which we

require 30 nivolumab‐treated patients (A’Hern single arm design,

80% power and a one‐sided 0.1 alpha). We expect to register 75‐120

patients during salvage treatment. Secondary endpoints are: safety

and tolerability of nivolumab (including safety of subsequent alloge-

neic transplant); progression free survival and overall survival at one

year. Exploratory endpoints include: correlating disease response

with baseline PD‐1 copy number, PD‐1 expression by IHC, immune

proﬁling of tumour and peripheral blood by ﬂow and gene expression

proﬁling; and assessment of whether response assessment can be

improved by combining PET with serum biomarkers e.g. TARC.

Since December 2018, 38 patients have been registered, of

whom 16 have been PET positive at the end of their current salvage

therapy and eligible for nivolumab.

Clinical trials.gov No. NCT03337919

The research was funded by: Bristol Myers Squibb

Keywords: Ongoing Trials

Conﬂicts of interests pertinent to the abstract

S. Barrington

Honoraria: Roche, Takeda

Educational grants: Takeda

C. Burton

Consultant or advisory role: Celgene, Bristol Myers Squibb

Foundation

Honoraria: Roche, Takeda

G. P. Collins

Consultant or advisory role: Roche, Takeda, Incyte, Pﬁzer, MSD,

Celgene, Beigene, Daiichi Sankyo, Celleron therpeutics, ADC

therapeutics

Honoraria: Roche, Takeda, Gilead Sciences, Pﬁzer, Novartis, Daiichi

Sankyo, Incyte, Celleron Therapeutics, MSD Oncology, BeiGene, ADC

Therapeutics

Research funding: MSD Oncology, Celegene, Celleron Therpeutics,

Bristol Myers Squibb, Amgen

Educational grants: Roche, Takeda

248 |BRENTUXIMAB VEDOTIN IN COMBINATION WITH

NIVOLUMAB, DOXORUBICIN, AND DACARBAZINE IN NEWLY

DIAGNOSED PATIENTS WITH ADVANCED HODGKIN

LYMPHOMA (SGN35‐027, TRIAL IN PROGRESS)

I. Flinn

, J. D. Friedman

, L. Ho

, H. J. Lee

Sarah Cannon Research Institute and Tennessee Oncology, Medical

Oncology, Nashville, Tennessee, USA,

University Hospitals, Seidman

Cancer Center, Cleveland, Ohio, USA,

Seagen Inc., Clinical Development,

Bothell, Washington, USA,

MD Anderson Cancer Center, Department of

Lymphoma & Myeloma, Houston, Texas, USA

Introduction: Brentuximab vedotin (BV) is approved for the treat-

ment of adults with treatment‐naïve Stage III or IV classical Hodgkin

lymphoma (cHL) in combination with doxorubicin, vinblastine, and

dacarbazine (AVD) (Connors 2017). Nivolumab is approved for

treatment of adults with relapsed/refractory cHL. Both agents have

been well tolerated with promising activity when combined with

multi‐agent chemotherapy. The combination of BV plus nivolumab

was evaluated as a frontline treatment option for patients (pts) with

cHL who are over 60 years and ineligible for or declined conventional

combination chemotherapy (Yasenchak 2020). The ongoing study

reported an overall response rate (ORR) of 82% in 11 pts and ap-

pears well tolerated in this population. In another trial in 93 pts in the

ﬁrst salvage setting, the combination produced a 67% complete

response (CR) rate (Herrera 2018, Moskowitz 2019) and the majority

of pts were able to undergo subsequent stem cell transplant. It is

reasonable to expect that the combination of BV, nivolumab, A, and D

(AN+AD) will result in high response rates and be well tolerated, with

potentially less toxicity relative to A+AVD.

Methods: SGN35‐027 (EudraCT 2020‐004027‐17) is an open‐label,

multiple part, multicenter, phase 2 clinical trial. Part A will evaluate

the efﬁcacy and safety of A+AVD when administered with growth

factor prophylaxis in pts with Stage III/IV cHL. Part B will evaluate

the combination of AN+AD in pts with Stage I or II cHL with bulky

mediastinal disease or Stage III or IV cHL. Part C will evaluate the

efﬁcacy and tolerability of AN+AD in pts with Stage I or II cHL

without bulky disease. The primary objective of Parts B and C is to

estimate the CR rate at end of treatment (EOT) in pts with treat-

ment‐naïve cHL.

Approximately 240 pts will be enrolled in this study: approxi-

mately 40 in Part A, 50 in Part B, and 150 in Part C. Part A has

completed enrollment, and Part B is fully enrolled. Pts in Parts B and C

will be treated with BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25

mg/m

, and dacarbazine 375 mg/m

, administered separately by IV

infusion on Days 1 and 15 of each 28‐day cycle. Pts in Part B will receive

up to 6 cycles of treatment; pts in Part C will receive 4 cycles. Efﬁcacy

will be assessed by PET/CT scans at Cycle 2 and EOT; disease response

and progression for Parts B and C will be assessed using the LYRIC

modiﬁcation of the Lugano Classiﬁcation Revised Staging System for

nodal non‐Hodgkin and Hodgkin lymphomas (Cheson 2016). Pts will be

followed for disease progression and overall survival for 5 years.

Enrollment is ongoing in the US, with plans for rest‐of‐world

expansion for Part C.

EA – previously submitted to ASCO 2021.

The research was funded by: Seagen Inc.

Keywords: Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

I. Flinn

SUPPLEMENT ABSTRACTS

339

Consultant or advisory role: Abbvie; AstraZeneca; BeiGene;

Gilead Sciences; Janssen; Juno Therapeutics; Kite Pharma; Mor-

phoSys; Nurix; Roche; Seagen Inc.; Shanghai Yingli Pharmaceuticals;

Takeda; TG Therapeutics; Unum Therapeutics; Verastem

Stock ownership: Johnson & Johnson

Research funding: Abbvie; Acerta Pharma; Agios; ArQule;

AstraZeneca; BeiGene; Calithera Biosciences; Celgene; Constellation

Pharmaceuticals; Curis; FORMA Therapeutics; Forty Seven; Gen-

entech; Gilead Sciences; Incyte; Inﬁnity Pharmaceuticals; Janssen;

Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Merck;

MorphoSys; Novartis; Pﬁzer; Pharmacyclics; Portola Pharmaceuti-

cals; Roche; Roche; Seagen Inc.; Takeda; Teva; TG Therapeutics;

Trillium Therapeutics; Unum Therapeutics; Verastem

J. D. Friedman

Consultant or advisory role: Celgene

Stock ownership: Abbott

Honoraria: Amgen; Celgene

Research funding: Seagen Inc./Astellas

L. Ho

Employment or leadership position: Seagen Inc.

Stock ownership: Seagen Inc.

Research funding: Seagen Inc.

Educational grants: Seagen Inc.

H. J. Lee

Consultant or advisory role: Bristol‐Myers Squibb; Guidepoint Global

Research funding: Bristol‐Myers Squibb; Celgene; Celgene; Oncter-

nal Therapeutics; Seagen Inc.; Takeda

249 |THE CLL‐RT1 TRIAL: A MULTICENTER PHASE‐2 TRIAL OF

ZANUBRUTINIB, A BTK INHIBITOR, PLUS TISLELIZUMAB, A PD‐1

INHIBITOR, FOR PATIENTS WITH RICHTER TRANSFORMATION

O. Al‐Sawaf

, S. Robrecht

, J. Stumpf

, A.‐M. Fink

, M. Ritgen

, P.

Johansson

, E. Tausch

, M. Hoechstetter

, P. Staber

, U. Jäger

, C. U.

Niemann

, C. Pallasch

, K.‐A. Kreuzer

, S. Stilgenbauer

, K. Fischer

C. Wendtner

, M. Hallek

, B. Eichhorst

University Hospital of Cologne, Department I of Internal Medicine,

Cologne, Germany,

University of Schleswig‐Holstein, Department II of

Internal Medicine, Kiel, Germany,

University Hospital Essen, Clinic for

Hematology, Essen, Germany,

University Hospital Ulm, Department III of

Internal Medicine, Ulm, Germany,

Klinikum Schwabing, Department of

Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases

and Tropical Medicine, Munich, Germany,

Medical University of Vienna,

Department of Medicine I, Division of Hematology & Hemostaseology,

Vienna, Austria,

Department of Haematology, Rigshospitalet and

Department of Clinical Medicine, University of Copenhagen, Denmark,

Copenhagen, Denmark

Introduction: Richter Transformation (RT) is deﬁned as trans-

formation of chronic lymphocytic leukemia (CLL) to diffuse large B

cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL). Overall prog-

nosis of patients with RT remains poor, with a median overall survival

of 6 ‐8 months after diagnosis. Given the high average age of patients

with CLL, many patients might not be eligible for intensive chemo-

immunotherapy at the time of RT and are therefore in need of

effective and tolerable treatment options. In light of early data sug-

gesting efﬁcacy of PD1 inhibitors and BTK inhibitors for patients with

RT, we designed an investigator‐initiated phase 2 study to test efﬁ-

cacy and safety of tislelizumab, a PD1 inhibitor, with zanubrutinib, a

BTK inhibitor for patients with CLL and RT.

Methods: Key inclusion criteria are diagnosis of CLL according to

iwCLL, histopathological diagnosis of RT (DLBCL or HL) and previ-

ously untreated RT, RT with objective response to ﬁrst‐line RT

treatment or non‐tolerance to prior line of RT treatment. Key

exclusion criteria are primary progressive disease, more than one

prior line of RT therapy and allogeneic stem cell transplantation up to

100 days prior to screening.

Each treatment cycle (à 21 days) consists of one infusion of 200

mg tislelizumab at day 1 and 160 mg zanubrutinib twice daily orally.

Six cycles of induction are followed by 6 cycles of consolidation;

patients with complete response (CR), partial response (PR) or stable

disease (SD) continue maintenance until disease progression or non‐

tolerance. Patients with response to treatment can undergo alloge-

neic transplantation any time after induction therapy.

The primary endpoint is overall response rate (ORR) after in-

duction therapy according to the reﬁned Lugano Classiﬁcation. Sec-

ondary endpoints include response according to iwCLL, progression‐

free survival and overall survival.

Efﬁcacy of the study treatment is assessed to be not effective if

the ORR is less than 40 % with corresponding null hypothesis H0:

ORR ≤0.40 and alternative hypothesis H1: ORR >0.40. It is assumed

to improve the ORR to at least 60 %. 48 eligible patients have to be

enrolled to achieve statistical signiﬁcance with a power of 80%.

The trial was initiated in January 2020 and aims to complete

recruitment within 2.5 years. So far, 18 patients have been enrolled.

10 centers in Germany, 1 site in Austria and 1 site Denmark are open

for enrolment. Potential patients can be discussed any time at CLL‐

Studie@uk‐koeln.de and +4922147888220.

The research was funded by: BeiGene

Keywords: OngoingTrials

Conﬂicts of interests pertinent to the abstract

O. Al‐Sawaf

Research funding: Beigene

A.‐M. Fink

Honoraria: Celgene, Janssen, Hoffmann‐LaRoche

M. Ritgen

Honoraria: Hoffmann‐LaRoche, AbbVie

Research funding: Hoffmann‐LaRoche,

U. Jäger

Honoraria: Novartis, Gilead, Celgene, Miltenyi, Janssen

340

SUPPLEMENT ABSTRACTS

Research funding: Novartis, Gilead, Celgene, Miltenyi, Janssen

C. U. Niemann

Research funding: Abbvie, Gilead, Janssen, Roche, CSL Behring,

Genmab, Sunesis, Astra Zeneca, Novo Nordisk Foundation

(NNF16OC0019302), Danish Ministry of Higher Education and

Science

K.‐A. Kreuzer

Honoraria: Hoffmann‐LaRoche, AbbVie

Research funding: Hoffmann‐LaRoche, AbbVie

S. Stilgenbauer

Honoraria: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La‐

Roche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem

Research funding: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoff-

mann La‐Roche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem

K. Fischer

Honoraria: AbbVie, Hoffmann‐LaRoche

C. Wendtner

Honoraria: Hoffmann‐LaRoche, AbbVie, Janssen‐Cilag, Gilead,

MorphoSys

M. Hallek

Honoraria: Roche, Gilead, Mundipharma, Janssen, Celgene, Pharma-

cyclics, AbbVie

Research funding: Roche, Gilead, Mundipharma, Janssen, Celgene,

Pharmacyclics, AbbVie

B. Eichhorst

Honoraria: Hoffmann‐LaRoche, Abbvie, Celgene, Novartis, ArQuele,

BeiGene, Gilead, AstraZeneca, Oxford Biomedica (UK), Adaptive

Biotechnologies

Research funding: Hoffmann‐LaRoche, AbbVie, Janssen

250 |PHASE 3 TRIAL (GCT3013‐05) OF EPCORITAMAB VERSUS

STANDARD OF CARE IN PATIENTS WITH RELAPSED OR

REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL)

C. Thieblemont

, M. R. Clausen

, A. S. Balari

, P. L. Zinzani

, C. P.

Fox

, S. Y. Kim

, S. D. Vindelov

, P. Lugtenburg

Assistance Publique & Hôpitaux de Paris (APHP), Hopital Saint‐Louis,

Université de Paris, Hemato‐Oncology Department, Paris, France,

Vejle

Hospital, Department of Hematology, Vejle, Denmark,

Institut Català

d'Oncologia‐Hospital Duran i Reynals IDIBELL, Universitat de Barcelona,

Hospitalet del Llobregat, Department of Hematology, Barcelona, Spain,

Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of

Hematology “L. e A. Seràgnoli,” University of Bologna, Department of

Experimental, Diagnostic and Specialty Medicine, Bologna, Italy,

Not-

tingham University Hospitals NHS Trust UK, Department of Clinical

Haematology, Nottingham, UK,

AbbVie, Clinical Development, North

Chicago, Illinois, USA,

Genmab, Clinical Development, Copenhagen,

Denmark,

On behalf of the HOVON/Lymphoma Working Group, Erasmus

MC Cancer Institute, Department of Hematology, Rotterdam, Netherlands

Background: Patients (pts) with DLBCL who are refractory to/or

have relapsed (R/R) after treatment with chemotherapy and anti‐

CD20 monoclonal antibody (mAb) have poor prognosis. New treat-

ment options are needed to improve outcomes. Epcoritamab, a novel

subcutaneous (SC) bispeciﬁc antibody, binds to CD3 on T‐

lymphocytes and CD20 on B‐cell non‐Hodgkin lymphoma (NHL)

cells. In an ongoing phase 1/2 dose‐escalation trial in heavily pre-

treated pts with B‐cell NHL (N =68), epcoritamab showed a tolerable

safety proﬁle and substantial single‐agent anti‐tumor activity, with a

complete response (CR) rate of 55% and an overall response rate of

91% in pts with R/R DLBCL (at ≥48 mg doses; n =12)

(NCT04663347; Hutchings, ASH, 2020). Furthermore, all 4 evaluable

R/R DLBCL pts previously treated with chimeric antigen receptor T‐

cell (CAR‐T) therapy achieved an objective response with 2 achieving

CR. These encouraging data support the potential for epcoritamab to

improve clinical outcomes in pts with R/R DLBCL. Here, we describe

the ongoing phase 3 trial of epcoritamab versus standard of care

(SOC) treatments in pts with R/R DLBCL.

Methods: GCT3013‐05 is a global, randomized, open‐label, multi-

center, phase 3 study designed to evaluate the efﬁcacy of epcor-

itamab versus investigator's choice of SOC with R‐GemOx

(rituximab, gemcitabine, oxaliplatin) or BR (bendamustine, rituximab)

in adults with R/R disease of one the following CD20+B‐cell NHL

histologies: I) DLBCL, not otherwise speciﬁed, including de novo

DLBCL or DLBCL histologically transformed from follicular lym-

phoma; II) “double or triple‐hit” DLBCL (high‐grade B‐cell lymphoma,

with MYC and BCL2 and/or BCL6 translocations), including de novo

SUPPLEMENT ABSTRACTS

341

“double‐hit” or “triple‐hit” DLBCL or “double‐hit” or “triple‐hit”

DLBCL histologically transformed from follicular lymphoma; or III)

follicular lymphoma grade 3B. Other key eligibility criteria include:

≥1 line of prior chemotherapy that included treatment with an anti‐

CD20 mAb, Eastern Cooperative Oncology Group performance sta-

tus 0–2, and prior failure of/ineligibility for autologous stem cell

transplantation. Prior CAR‐T therapy is allowed. A total of 480 pts

will be randomized 1:1 to receive either SC epcoritamab or up to 4

cycles of biweekly treatment with intravenous (IV) R‐GemOx (8

doses); or up to 6 cycles of IV BR (6 doses; dosing every 3 weeks).

Epcoritamab will be given at the recommended phase 2 dose in 28‐

day cycles: weekly, biweekly, or monthly schedule depending on cy-

cle number. Treatment is administered until disease progression or

unacceptable toxicity. The primary endpoint is overall survival. Key

secondary endpoints include progression‐free survival, overall

response rate, duration of response, time to response, and safety. The

study is currently enrolling in Australia, Belgium, Denmark, France,

Spain, and will open for enrollment in additional countries

(NCT04628494).

EA – previously submitted to ASCO 2021.

The research was funded by: Genmab A/S and AbbVie Inc.

Keywords: Ongoing Trials

Conﬂicts of interests pertinent to the abstract

C. Thieblemont

Consultant or advisory role: Celgene, Roche, Novartis, and Janssen

Honoraria: Gilead Sciences, Novartis, Celgene, Roche, and Janssen

Research funding: Roche

Educational grants: Novartis, Roche, Gilead Sciences, and Janssen

M. R. Clausen

Consultant or advisory role: Janssen, AbbVie, Gilead

Educational grants: Gilead, AbbVie

C. P. Fox

Honoraria: Genmab, Roche, Celgene/BMS, AbbVie, Morphosys,

Incyte, Atrarbio, Astrazeneca, Takeda, Gilead

Other remuneration: Research Grants: Roche, AbbVie, Takeda, Gilead

P. Lugtenburg

Other remuneration: Takeda, Servier, Roche, Genmab, Celgene,

Regeneron, Incyte

251 |PHASE 3 RANDOMIZED STUDY OF LONCASTUXIMAB

TESIRINE PLUS RITUXIMAB VERSUS IMMUNOCHEMOTHERAPY

IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B‐

CELL LYMPHOMA – LOTIS‐5

C. CARLO‐STELLA

, Y. Linhares

, M. D. Gandhi

, M. Chung

, H.

Adamis

, D. Ungar

, M. Hamadani

Humanitas Clinical and Research Center ‐IRCCS, and Humanitas

University, Department of Oncology and Hematology, Rozzano, Milan,

Italy,

Miami Cancer Institute, Baptist Health, Medical Oncology, Miami,

USA,

Virginia Cancer Specialists, Medical Oncology, Gainesville, USA,

The Oncology Institute of Hope and Innovation, Hematology/Oncology,

Downey, USA,

ADC Therapeutics SA, Clinical Development, Epalinges,

Switzerland,

ADC Therapeutics America, Inc, Clinical Development,

Murray Hill, USA,

Medical College of Wisconsin, Division of Hematology

and Oncology, Milwaukee, USA

Introduction: Patients (pts) with diffuse large B‐cell lymphoma

(DLBCL) for whom frontline therapy is unsuccessful and who are

ineligible for autologous stem cell transplantation (SCT) have poor

outcomes with salvage therapy. Single‐agent loncastuximab tesirine

(Lonca), an antibody‐drug conjugate comprising a humanized anti‐

CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine

dimer toxin, showed antitumor activity and manageable toxicity in

pts with relapsed/refractory (R/R) B‐cell non‐Hodgkin lymphoma in a

Phase 1 trial (Hamadani et al. Blood 2020; blood.2020007512) and in

pts with R/R DLBCL in a Phase 2 trial (Caimi et al. Blood 2020; 136

(Suppl 1):35–37).

Rituximab (R) is part of standard immunochemotherapy for

DLBCL, both as frontline therapy and in subsequent treatments.

LOTIS‐5 aims to evaluate Lonca +R (Lonca‐R) versus (vs) standard

immunochemotherapy of R +gemcitabine +oxaliplatin (R‐GemOx) in

pts with R/R DLBCL.

Methods: This is a Phase 3 randomized, open‐label, 2‐part, 2‐arm,

multicenter study (NCT04384484). A non‐randomized safety run‐in

(Part 1) will compare the safety of Lonca‐R with previous safety

data for Lonca after the ﬁrst 20 pts have completed Cycle 1. Part 2

will be started if no signiﬁcant increase in toxicity occurs; ∼330 pts

will be randomized 1:1 to receive Lonca‐R or R‐GemOx.

The primary objective of the study is to evaluate the efﬁcacy of

Lonca‐R vs R‐GemOx. The primary endpoint is progression‐free

survival by independent review. Secondary endpoints include over-

all survival; objective response rate; complete response rate; dura-

tion of response; frequency and severity of adverse events; changes

from baseline in safety laboratory and clinical variables; concentra-

tion and pharmacokinetic parameters of Lonca (conjugated and total

antibody, and unconjugated warhead); immunogenicity; and changes

in patient‐reported outcomes. Time‐to‐event endpoints will be

assessed for the intent‐to‐treat population using a stratiﬁed log rank

test. The dosing regimen of Lonca‐R in both parts of the study will be

150 µg/kg Lonca +375 mg/m

R every 3 weeks (Q3W) for 2 cycles

and then 75 µg/kg Lonca +375 mg/m

R for 6 cycles. The dose

regimen of R‐GemOx in Part 2 will be 375 mg/m

R, 1000 mg/m

Gem, and 100 mg/m

Ox Q2W for 8 cycles.

Key inclusion criteria include age ≥18 years; pathologic diagnosis

of DLBCL (including pts with DLBCL transformed from indolent lym-

phoma) or high‐grade B‐cell lymphoma with MYC and BCL2 and/or

BCL6 rearrangements; ≥1 line of prior systemic therapy; not a candi-

date for SCT; and measurable disease per 2014 Lugano Classiﬁcation.

The study opened in September 2020 and enrollment is ongoing.

The trial design was presented at 62nd American Society of

Hematology Annual Meeting and Exposition, December 5–8, 2020.

342

SUPPLEMENT ABSTRACTS

Encore abstract ‐previously submitted to ASH 2020 (before

enrollment started); current abstract submitted to ASCO and EHA

2021.

permission. This abstract was accepted and previously presented at

The research was funded by: The research was funded by ADC

Therapeutics SA

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination

Therapies, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

C. CARLO‐STELLA

Consultant or advisory role: Sanoﬁ, ADC Therapeutics, Roche, Kar-

yopharm Therapeutics, Celgene/Bristol‐Myers Squibb, Incyte

Honoraria: Bristol‐Myers Squibb, Merck Sharp & Dohme, Janssen

Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead Sciences

Research funding: ADC Therapeutics, Sanoﬁ, Roche

Educational grants: Roche, Janssen, Takeda, ADC Therapeutics

M. D. Gandhi

Consultant or advisory role: GSK

H. Adamis

Employment or leadership position: Fresenius Kabi BioSim, ADC

Therapeutics

D. Ungar

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

M. Hamadani

Consultant or advisory role: MedImmune, Cellerant Therapeutics,

Janssen, Incyte, Pharmacyclics, ADC Therapeutics, Puma Biotech-

nology, Verastem

Honoraria: Celgene

Research funding: Takeda, Spectrum Pharmaceuticals, Otsuka US,

Astellas Pharma, Genzyme

Other remuneration: Genzyme (Speaker's bureau), Celgene

(Speaker's bureau), AstraZeneca (Speaker's bureau)

252 |ESCALADE: A PHASE 3 STUDY OF ACALABRUTINIB IN

COMBINATION WITH R‐CHOP FOR PATIENTS ≤65Y WITH

UNTREATED NON‐GERMINAL CENTER B‐CELL–LIKE DIFFUSE

LARGE B‐CELL LYMPHOMA

L. H. Sehn

, B. Kahl

, M. Matasar

, G. Lentz

, K. Izutsu

, W. Zhao

L. Tao

, R. Calvo

, P. L. Zinzani

BC Cancer Centre for Lymphoid Cancer, Medical Oncology, Vancouver,

Canada,

Washington University in St. Louis, Oncology, St. Louis, Missouri,

USA,

Memorial Sloan Kettering Cancer Center, Medical Oncology Service,

New York, New York, USA,

University Hospital Münster, Medicine A –

Haematology and Oncology, Münster, Germany,

National Cancer Center

Hospital, Hematology, Tokyo, Japan,

Shanghai Institute of Haemato‐

oncology, Hematology, Shanghai, China,

AstraZeneca, Biostatistics, South

San Francisco, California, USA,

AstraZeneca, Clinical Development He-

matology, R&D Oncology, Gaithersburg, Maryland, USA,

Institute of

Hematology “Seràgnoli” University of Bologna, Experimental, Diagnostic

and Specialty Medicine ‐DIMES, Bologna, Italy

Background: Rituximab, cyclophosphamide, doxorubicin, vincristine,

and prednisone (R‐CHOP) remains the standard of care for diffuse

large B‐cell lymphoma (DLBCL). Although most patients (pts) can

be cured, 35–40% will experience relapsed/refractory disease,

leading to poor outcomes in the majority of pts. Covalent irre-

versible Bruton tyrosine kinase inhibitors (BTKi) have shown

higher responses in pts with non‐germinal center B‐cell–like (non‐

GCB) DLBCL than with GCB DLBCL. In untreated non‐GCB DLBCL

pts, the phase 3 PHOENIX study (Younes et al. J Clin Oncol.

2019;37:1285‐95) showed that addition of the BTKi ibrutinib to R‐

CHOP (R‐CHOP‐I) did not improve outcomes in the intent‐to‐treat

population. However, pts age <60y treated with R‐CHOP‐I had

signiﬁcantly improved progression‐free survival (PFS) and overall

survival (OS) compared with those receiving R‐CHOP alone. Aca-

labrutinib (A) is a second‐generation BTKi with enhanced kinase

selectivity and potential for better efﬁcacy and tolerability than

ﬁrst‐generation BTKis. There is a strong rationale for combining A

with R‐CHOP in pts with untreated DLBCL, and safety of A +R‐

CHOP has been shown in a phase 1b/2 study (Davies et al. ASH

2020). The aim of this study is to determine if the addition of A to

R‐CHOP leads to improved PFS in pts age ≤65y with untreated

non‐GCB DLBCL.

Methods: ESCALADE (ACE‐LY‐312; NCT04529772) is a phase 3,

randomized, global, double‐blind study of A vs placebo in combi-

nation with R‐CHOP for treatment of newly diagnosed non‐GCB

DLBCL. The study is recruiting adults ≥18y and ≤65y with previ-

ously untreated DLBCL stage II–IV disease with a Revised Inter-

national Prognostic Index (R‐IPI) score of 2–5. Prior to

randomization, all pts will receive an initial R‐CHOP cycle (cycle 1)

as standard‐of‐care treatment to prevent delays in therapy initia-

tion. Based on central Gene Expression Proﬁle (GEP) testing per-

formed after enrollment, pts with non‐GCB DLBCL (activated B‐cell

like or unclassiﬁed) will be randomized into 2 arms to receive A 100

mg twice daily plus R‐CHOP or placebo plus R‐CHOP from cycle 2

to cycle 6 followed by 2 additional cycles of rituximab +A or pla-

cebo (cycles 7 and 8). All pts will receive primary prophylaxis with

granulocyte colony‐stimulating factors accompanying all R‐CHOP

cycles. The study aims to randomize 600 pts (∼300 per arm). The

primary objective is to evaluate whether the addition of A to R‐

CHOP will prolong PFS. Secondary endpoints include event‐free

survival, complete response rate, OS, pharmacokinetics, and

safety. Key exclusion criteria are central nervous system involve-

ment, primary mediastinal lymphoma, high‐grade B‐cell lymphoma,

diagnosis or treatment of malignancy other than DLBCL, and history

of indolent lymphoma. Approximately 250 sites globally will enroll

pts. Enrollment began in Q3 of 2020.

SUPPLEMENT ABSTRACTS

343

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: Acerta Pharm, a member of the

AstraZeneca Group

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Molecular

Targeted Therapies, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

L. H. Sehn

Consultant or advisory role: Celgene, AbbVie, Seattle Genetics, TG

Therapeutics, Janssen, Amgen, Roche/Genentech, Gilead Sciences,

Lundbeck, Amgen, Apobiologix, Karyopharm Therapeutics, Kite

Pharma, Merck, Takeda, Teva, AstraZeneca, Acerta Pharma, Mor-

phosys, Incyte, Debiopharm Group, Sandoz‐Novartis, Genmab,

Verastem

Honoraria: Amgen, Apobiologix, AbbVie, Celgene, Gilead Sciences,

Janssen‐Ortho, Karyopharm Therapeutics, Kite Pharma, Lundbeck,

Merck, Roche/Genentech, Seattle Genetics, Takeda, Teva, TG Ther-

apeutics, AstraZeneca, Acerta Pharma, Morphosys, Incyte, Debio-

pharm Group, Sandoz‐Novartis, Verastem, Genmab, AstraZeneca

Research funding: Roche/Genentech, Teva

B. Kahl

Consultant or advisory role: Celgene, AbbVie, Pharmacyclics, Acerta

Pharma, ADC Therapeutics, Genentech, Roche, BeiGene, Bayer, MEI

Pharma, Kite/Gilead, MorphoSys, Janssen, Karyopharm Therapeutics,

Teva, BMS, Molecular Templates, Incyte

Research funding: Genentech, Acerta Pharma, ADC Therapeutics,

Celgene

Educational grants: Celgene, Juno Therapeutics, Genentech/Roche,

AbbVie, Millenium, Seattle Genetics

M. Matasar

Consultant or advisory role: Genentech, Bayer, Merck, Juno Thera-

peutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi San-

kyo, Takeda;

Stock ownership: Merck

Honoraria: Genentech, Roche, Glaxosmithkline, Bayer, Pharmacy-

clics, Janssen, Seattle Genetics, Immunovaccine Technologies, Takeda

Research funding: Genentech, Roche, Glaxosmithkline, IGM Bio-

sciences, Bayer, Pharmacyclis, Janssen, Rocket Medical, Seattle GE-

netics, Immunovaccine Tech

Educational grants: Genentech, Roche, Seattle Genetics, Bayer

Other remuneration: Expert Testimony: Bayer

G. Lentz

Consultant or advisory role: Roche/Genentech, Janssen‐Cilag,

Bristol‐Myers Squibb, Bayer, Novartis, Celgene, MorphoSys, Astra-

Zeneca, Gilead Sciences

Honoraria: Janssen‐Cilag, Bayer, Celgene, Roche/Genentech, Astra-

Zeneca, BMS, MorphoSys, Gilead Sciences, Novartis, AbbVie

Research funding: Janssen‐Cilag, Roche/Genentech, AstraZeneca,

Aquinox Pharmaceuticals, Bayer, MorphoSys, Gilead Sciences, Vera-

stem, AGIOS

Educational grants: Janssen‐Cilag, Celegene, AstraZeneca, Roche/

Genentech,

Other remuneration: Expert Testimony: MorphoSys

K. Izutsu

Consultant or advisory role: Bayer, Celgene, AstraZeneca, Ono

Pharmaceutical, Kyowa Kirin

Honoraria: Takeda, Chugai Pharma, Eisai, Janssen, AbbVie, Novartis,

MSD, Sumitomo Dainippon Pharma, Ono Pharmaceutical, Mundi-

pharma, HUYA Bioscience International, AstraZeneca, Bayer, BMS,

Kyowa Kirin, Fujiﬁlm, Celgene, Daiichi Sankyo, Allergan

Research funding: Eisai, Chugai Pharma

L. Tao

Employment or leadership position: AstraZeneca

R. Calvo

Employment or leadership position: AstraZeneca

Stock ownership: AstraZeneca

P. L. Zinzani

Consultant or advisory role: Verastem, Celltrion, Gilead, Janseen‐

Cilag, BMS, Servier, Sandoz, MSD, TG Therapeutics, Takeda, Roche,

Eusapharma, Kwoya Kirin, Sanoﬁ, ADC Therapteutics

Other remuneration: Speakers’ Bureau ‐Verastem, Celltrion, Gilead,

Janseen‐Cilag, BMS, Servier, MSD, TG Therapeutics, Takeda, Roche,

Eusapharma, Kyowa Kirin

253 |A PHASE III TRIAL OF GLOFITAMAB PLUS GEMCITABINE

AND OXALIPLATIN (GEMOX) VS RITUXIMAB PLUS GEMOX FOR

RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA

M. Hertzberg

, M. Ku

, O. Catalani

, B. Althaus

, S. Simko

, G. P.

Gregory

Prince of Wales Hospital, Department of Hematology, Sydney, Australia,

St.Vincent's Hospital, The University of Melbourne, Department of

Haematology, Melbourne, Australia,

F. Hoffmann‐La Roche Ltd, Statis-

tics, Basel, Switzerland,

Genentech, Inc., Product Development Hema-

tology, South San Francisco, USA,

School of Clinical Sciences at Monash

Health, Monash University, Department of Clinical Haematology, Mel-

bourne, Australia

Introduction: Prognosis is poor for patients with relapsed/refractory

(R/R) diffuse large B‐cell lymphoma (DLBCL), particularly those who

are ineligible for autologous stem cell transplant (ASCT) or who

relapse after second‐line therapy (Gisselbrecht C, et al. Br J Hae-

matol 2018). While chimeric antigen receptor therapies have shown

favorable response rates in R/R DLBCL, convenient off‐the‐shelf

options are needed, especially for patients with rapidly progressing

disease (Sermer D, et al. Blood Adv 2020). Gloﬁtamab is a full‐length,

humanized immunoglobulin G1 bispeciﬁc antibody with two regions

that bind to CD20 (B cells) and one region that binds to CD3 (T cells).

In an ongoing Phase I study in patients with R/R non‐Hodgkin

344

SUPPLEMENT ABSTRACTS

lymphoma, gloﬁtamab monotherapy has induced high response rates

with a manageable safety proﬁle (NCT03075696; Hutchings M, et al.

ASH 2020). Rituximab in combination with GemOx (R‐GemOx) is

widely used for patients with R/R DLBCL who are not eligible for

ASCT (Mounier N, et al. Haematologica 2013).

Methods: GO41944 (NCT04408638) is a Phase III, open‐label, ran-

domized trial designed to evaluate the safety and efﬁcacy of gloﬁ-

tamab plus gemcitabine and oxaliplatin (gloﬁt‐GemOx) vs R‐GemOx

in patients with R/R DLBCL. Eligible patients must be aged ≥18 years,

have histologically conﬁrmed DLBCL (excluding transformed indolent

disease, and high‐grade B‐cell lymphoma (BCL) with MYC and BCL2

and/or BCL6 rearrangements), and have received ≥1 prior systemic

therapies; patients who have failed only one prior line of therapy

must not be eligible for high‐dose chemotherapy followed by ASCT.

Prior treatment with GemOx, R‐GemOx or a CD20xCD3 bispeciﬁc

antibody is not permitted. Patients are randomized 2:1 to receive up

to eight 21‐day cycles of either gloﬁt‐GemOx (intravenous [IV], fol-

lowed by up to four cycles of gloﬁtamab monotherapy) or R‐GemOx

(IV). A single dose of obinutuzumab is administered seven days prior

to the ﬁrst gloﬁtamab administration. Randomization is stratiﬁed by

number of prior lines of therapy and outcome of last systemic ther-

apy (relapsed vs refractory). The primary objective is overall survival

from time of randomization. Secondary efﬁcacy objectives include

progression‐free survival, complete and overall response rates,

duration of response, and time to deterioration in physical func-

tioning and fatigue, and in lymphoma symptoms. Safety objectives

comprise rate of adverse events, change from baseline in targeted

vital signs and clinical laboratory test results, and tolerability. Phar-

macokinetic, immunogenicity and biomarker endpoints will also be

explored. The study started on February 17, 2021; an estimated

enrollment of 270 patients by the study completion date of March

2022 is anticipated.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: F. Hoffmann‐La Roche Ltd/Genentech,

Inc. Third‐party medical writing assistance, under the direction of the

authors, was provided by Katie Buxton, PhD, of Ashﬁeld MedComms,

an Ashﬁeld Health company, and was funded by F. Hoffmann‐La

Roche Ltd/Genentech, Inc.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

M. Hertzberg

Consultant or advisory role: Takeda, Gilead, F. Hoffmann‐La Roche

Ltd, MSD

Honoraria: F. Hoffmann‐La Roche Ltd, Janssen, Takeda, Bristol‐

Myers Squibb

Research funding: F. Hoffmann‐La Roche Ltd, Janssen, GSK

M. Ku

Consultant or advisory role: F. Hoffmann‐La Roche Ltd, Antengene

Research funding: Karyopharm

O. Catalani

Employment or leadership position: F. Hoffmann‐La Roche Ltd

B. Althaus

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

S. Simko

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

G. P. Gregory

Consultant or advisory role: F. Hoffmann‐La Roche Ltd, Novartis/

Sandoz, Janssen, Gilead

Honoraria: F. Hoffmann‐La Roche Ltd

Research funding: F. Hoffmann‐La Roche Ltd, BeiGene, MSD, AbbVie,

Janssen

Educational grants: F. Hoffmann‐La Roche Ltd, Novartis

Other remuneration: Speakers' bureau: F. Hoffmann‐La Roche Ltd;

Expert testimony: Janssen

254 |BRENTUXIMAB VEDOTIN IN COMBINATION WITH

LENALIDOMIDE AND RITUXIMAB IN SUBJECTS WITH RELAPSED

OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL)

(TRIAL IN PROGRESS)

N. L. Bartlett

, C. A. Yasenchak

, K. K. Ashraf

, W. N. Harwin

, R. B.

Sims

, G. S. Nowakowski

Washington University School of Medicine, Division of Oncology, St.

Louis, Missouri, USA,

Willamette Valley Cancer Institute and Research

Center/US Oncology Research, Medical Oncology, Hematology,

Springﬁeld, Oregon, USA,

Hematology and Oncology Associates of

Alabama, Medical Oncology, Hematology, Birmingham, Alabama, USA,

Sarah Cannon Research Institute, Hematology and Oncology, Fort

Meyers, Florida, USA,

Seagen Inc., Clinical Development, Bothell,

Washington, USA,

Mayo Clinic, Division of Hematology, Rochester,

Minnesota, USA

Introduction: The majority of patients (pts) with relapsed/refractory

(R/R) diffuse large B‐cell lymphoma (DLBCL) who relapse after HSCT

or CAR‐T, or who are not candidates for HSCT or CAR‐T have poor

outcomes and are in need of novel therapies. Brentuximab vedotin

(BV) is a CD30‐directed ADC and preclinical data provide a strong

rationale for combining BV, lenalidomide, and rituximab in the

treatment of R/R DLBCL. In addition, in a phase 1 trial in which 37

pts with R/R DLBCL were treated with BV +lenalidomide, the ORR

was 56.7% (73.3% in CD30+pts; manuscript in preparation). The

median duration of remission was 13.2 months in pts with a CR or

PR and 11.7 months in pts with CR, PR, or stable disease >6 months.

The PFS and median OS were 11.2 months and 14.3 months,

respectively and results were similar in the CD30+and CD30 <1%

groups. The clinical activity and manageable safety proﬁles of

BV, lenalidomide, and rituximab as single agents, make the combi-

nation a potentially viable option in multiply relapsed and heavily

pretreated pts.

SUPPLEMENT ABSTRACTS

345

Methods: This is a randomized, double‐blind, placebo‐controlled,

active‐comparator, multicenter phase 3 study designed to evaluate the

efﬁcacy of BV vs placebo, in combination with lenalidomide +ritux-

imab, in subjects with R/R DLBCL (EudraCT: 2020‐002686‐33). Prior

to randomization, there will be a safety and PK run‐in period where 6

pts will receive BV, lenalidomide +rituximab, and safety and PK will be

evaluated after the ﬁrst cycle of treatment; 6/6 subjects have been

enrolled.

Key eligibility criteria include: pts aged ≥18 with R/R DLBCL

with an eligible subtype; ≥2 prior lines of therapy and have relapsed,

declined, or are ineligible for stem cell transplant, or chimeric antigen

receptor T‐cell (CAR‐T) therapy; ECOG 0 to 2; ﬂuorodeoxyglucose‐

avid disease by PET and bidimensional measurable disease of at

least 1.5 cm by CT.

Patients (n =400) will be randomized 1:1 to receive either BV or

placebo in combination with lenalidomide +rituximab and will be

stratiﬁed by CD30 expression (positive [≥1%] versus <1%), prior

allogeneic or autologous stem cell transplant therapy (received or not),

prior CAR‐T therapy (received or not), and cell of origin (GCB or non‐

GCB).

The primary endpoints are PFS per BICR in the ITT and CD30+

populations. Key secondary endpoints are OS in the ITT and CD30+

populations, and ORR per BICR. Other secondary endpoints include

CR rate, duration of response, and safety and tolerability of the

combination. Disease response will be assessed by BICR and the

investigator according to the Lugano Classiﬁcation Revised Staging

System. Radiographic disease evaluations, including contrast‐

enhanced CT scans and PET, will be assessed at baseline, then

every 6 weeks from randomization until Week 48, then every 12

weeks. PET is not required after CR is achieved.

The trial is currently enrolling and will be open in 16 countries.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: Seagen Inc.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination

Therapies, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

N. L. Bartlett

Consultant or advisory role: Seagen Inc., Roche/Genentech, ADC

Therapeutics, BTG, Acerta Pharma

Research funding: Seagen Inc., Kite Pharma, Merck, Bristol‐Myers

Squibb, Celgene, Immune Design, Forty Seven, Janssen, Pharmacy-

clics, Millennium, ADC Therapeutics, Autolus, Roche/Genentech,

Pﬁzer, Afﬁrmed Therapeutics

C. A. Yasenchak

Consultant or advisory role: BeiGene

Stock ownership: Karyopharm Therapeutics

Honoraria: Seagen Inc., Takeda

Research funding: Seagen Inc.

W. N. Harwin

Research funding: Sarah Cannon Research Institute

R. B. Sims

Employment or leadership position: Seagen Inc.

G. S. Nowakowski

Consultant or advisory role: Celgene, MorphoSys, Genentech, Selvita,

Debiopharm Group, Kite/Gilead

Research funding: Celgene, NanoString Technologies, MorphoSys

255 |COPANLISIB IN COMBINATION WITH RITUXIMAB‐

BENDAMUSTINE IN PATIENTS WITH RELAPSED‐REFRACTORY

DLBCL: A MULTICENTRIC PHASE II TRIAL OF THE FONDAZIONE

ITALIANA LINFOMI

M. Novo

, A. Castellino

, A. Chiappella

, G. Ciccone

, M. Balzarotti

A. Di Rocco

, M. Spina

, U. Vitolo

FPO‐IRCCS Candiolo Cancer Institute, Multidisciplinary Oncology

Outpatient Clinic, Candiolo (TO), Italy,

Santa Croce e Carle Hospital,

Hematology Unit, Cuneo, Italy,

Fondazione IRCCS Istituto Nazionale dei

Tumori di Milano, Division of Hematology and Stem Cell Transplantation,

Milano, Italy,

Azienda Ospedaliero‐Universitaria Città della Salute e della

Scienza di Torino, Unit of Clinical Epidemiology and CPO, Torino, Italy,

Humanitas Clinical and Research Hospital IRCCS , Hematology Unit,

Rozzano (Milano), Italy,

Università La Sapienza, Department of Trans-

lational and Precision Medicine, Roma, Italy,

National Cancer Institute,

Division of Medical Oncology, Aviano, Italy

Introduction: Diffuse large B cell lymphoma (DLBCL) is a curable

disease in 50‐60% of cases with frontline immunochemotherapy.

Salvage strategies for relapsed/refractory (R/R) DLBCL are able to

cure 40‐50% of patients (pts), and include high dose‐chemotherapy +

autologous stem cell transplant (ASCT) and chimeric antigen receptor

T‐cells (CART), the latter allowed after ≥2 prior lines of treatment in

pts with no major comorbidities. Thus, new strategies for R/R DLBCL

unresponsive or ineligible to ASCT or CART are warranted. Ritux-

imab +bendamustine (RB) is active in R/R DLBCL but response is

usually of short duration. Copanlisib is an intravenous pan‐class I

PI3K inhibitor with predominant activity against PI3K‐α and ‐δ iso-

forms, active as monotherapy in indolent lymphomas (iNHL) and

DLBCL with overall response rates (ORR) of 59% and 25%, respec-

tively (NCT01660451)(NCT02391116). Transient hyperglycemia and

transient hypertension are the most frequent treatment‐emergent

adverse events. The association of copanlisib +RB (Copa‐RB)

showed a safe toxicity proﬁle when tested on R/R iNHL

(NCT02626455). The aim of this trial is to evaluate safety and efﬁ-

cacy of Copa‐RB followed by copanlisib maintenance in R/R DLBCL

not eligible or relapsed after ASCT or CART.

Methods: This is a multicentric open‐label single arm, single stage,

phase II trial. An estimated 81 pts will be enrolled, from 30 centers in

Italy. Main inclusion criteria are pts aged ≥18 affected by DLBCL

(including de‐novo DLBCL, DLBCL transformed by iNHL and high‐

grade lymphoma) R/R after ≤3 previous lines of therapy, ineligible

or R/R to ASCT or CART, ECOG performance status 0‐2. Primary

346

SUPPLEMENT ABSTRACTS

mediastinal B cell lymphoma are excluded. Treatment include an in-

duction phase with six 28‐day cycles of copa‐RB (copanlisib 60 mg

intravenously on day (D) 1, D8 and D15, rituximab 375 mg/m

on D1,

bendamustine 90 mg/m

on D1‐D2) followed by a maintenance

phase of twelve 28‐day cycles of copanlisib 60 mg given on D1 and

D15 (Figure). The primary endpoint is progression free survival (PFS),

with an expected improvement of 12‐month PFS from 20% to 35%.

Secondary endpoints include overall survival, ORR, complete

response rate, duration of response and rate of response improve-

ment during maintenance. Exploratory analysis will include correla-

tion between outcome and cell of origin, MYC, BCL2 and BCL6

overexpression and rearrangements, and mutational analysis of

selected genes possibly involved in predicting response to copanlisib.

The expected study duration from ﬁrst pts's enrollment to last pts's

last visit is approximately 4 years. The recruitment started in

November 2020 and at March 12th 8/81 pts have been enrolled.

Results for this study are not yet available. Clinical trial information:

NCT04433182

The research was funded by: The study is sponsored by Fondazione

Italiana Linfomi. The study is partially supported by Bayer

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination

Therapies, Ongoing Trials

No conﬂicts of interests pertinent to the abstract.

256 |A PHASE II STUDY OF ANTI‐PD‐1 SINTILIMAB IN

COMBINATION WITH CHIDAMIDE AND AZACITIDINE IN

REFRACTORY AND RELAPSED PERIPHERAL T‐CELL LYMPHOMA

Z. Ying

, Y. Song

, X. Wang

, N. Lin

, Y. Xie

, T. Du

, Y. Tang

, J. Zhu

Peking University Cancer Hospital & Institute, Key Laboratory of

Carcinogenesis and Translational Research (Ministry of Education/Beijing),

Department of Lymphoma, Beijing, China

Background: Peripheral T‐cell lymphomas (PTCLs) are a highly

heterogeneous group of aggressive malignant lymphomas, usually

exhibit a poor prognosis, with a 5‐year survival <50%, the risk of

relapse remains quite high and relapsed or refractory (R/R) patients

have been shown to have a very dismal outcome. Immunotherapy

with anti‐PD‐1 antibodies may help the body's immune system attack

the cancer, and may interfere with the ability of tumor cells to grow

and spread. So far the largest study (Gxplore‐002) including 102

patients with R/R PTCL showed that anti‐PD‐1 antibody is safe and

has promising activity with overall response rate (ORR) of 40.4%.

However, the depth of remission and long term prognosis are not

satisﬁed with complete response rate (CRR) of 14.6% and the median

progression‐free survival of 2.7 months. Combination therapy is a

potential strategy to increase the efﬁcacy. Epigenetic agents may

promote effect of anti‐PD‐1 antibody by stimulating antigen pre-

sentation, enhancing the migration of T cells to the tumor microen-

vironment, restoring T cell activation. These rationales support the

combination of anti‐PD‐1 antibody and epigenetic agents. Therefore,

the combination of sintilimab (anti‐PD‐1 antibody) and chidamide

(histone deacetylase inhibitors, HDACi), azacitidine (hypomethylating

agents, HMA) may have potent synergy in treating patients with

relapsed or refractory PTCLs.

Methods: This is a single‐arm‐phase II clinical trial for patients with

relapsed or refractory PTCLs. Patients with at least one line of

standard therapy are required. Prior HDACi or PD‐1/PD‐L1 anti-

bodies or HMA is allowed. Patients with CNS disease or cutaneous T‐

cell lymphoma are excluded. Eligible patients will be treated with

sintilimab (200 mg IV Q3W on day 1) in combination with chidamide

(30 mg PO BIW on d1 and d4) and azacitidine (100 mg SC Q3W days

1‐7). Cycles repeat every 3 weeks for up to 24 months in the absence

of disease progression, death, unacceptable toxicity, hematopoietic

stem cell transplantation, withdrawal of informed consent, other

reasons speciﬁed in the protocol or the decision of the researcher.

After completion of study treatment, participants are followed up at

90 days for safety and then every 90 days for survival. The study

intends to enroll approximately 30 patients. Considering the safety of

patients, the ﬁrst 6 patients will be recruited slowly, if a DLT is

observed in 2 of 6 patients, the investigators will decide to reduce

the dose of chidamide to 20 mg, otherwise, all patients use 30 mg

SUPPLEMENT ABSTRACTS

347

chidamide. The primary objective is ORR; the secondary objectives

are CRR, duration of response (DOR), progression‐free survival (PFS),

overall survival(OS) and adverse events; the exploratory objective is

the correlation of clinical response with the expression of PD‐L1,

CD4, CD8, CD68 in tumor environment. Clinical trial information:

NCT04052659

The research was funded by: Innovent Biologics Inc.

Keywords: Combination Therapies, Immunotherapy, Aggressive T‐

cell non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

257 |AN OPEN‐LABEL TRIAL OF ORAL CA‐4948 AN IRAK4

INHIBITOR COMBINED WITH IBRUTINIB IN ADULT PATIENTS

WITH RELAPSED OR REFRACTORY HEMATOLOGIC

MALIGNANCIES

E. Joffe

, R. Ramchandren

, G. Nowakowski

, A. Rosenthal

, H. W.

Tun

, M. Lunning

, M. D. Mead

, E. Martinez

, R. von Roemeling

, L.

Leslie

Memorial Sloan Kettering Cancer Center, Hematology Oncology‐

Lymphoma Services, NY, New York, USA,

University of Tennessee

Medical Center‐University Cancer Specialists, Hematology, Medical

Oncology, Knoxville, Tennessee, USA,

Mayo Clinic‐Minnesota, Rochester,

MN, Hematology ‐Cancer Center, Rochester, Minnesota, USA,

Mayo

Clinic‐Arizona, Hematology, Phoenix, Arizona, USA,

Mayo Clinic, Florida,

Hematology Oncology‐Caner Center, Jacksonville, Florida, USA,

Uni-

versity of Nebraska, Division of Oncology & Hematology, Omaha,

Nebraska, USA,

University of California Los Angeles‐Santa Monica

Medical Center, Medicine, Hematology and Oncology, Santa Monica ,

California, USA,

Curis, Clinical Development, Lexington, Massachusetts,

USA,

John Theurer Cancer Center, Hackensack, NJ, Hematology

Oncology, Hackensack, New Jersey, USA

Introduction: Interleukin‐1 receptor‐associated kinase 4 (IRAK4) is

essential for toll‐like receptor (TLR) and interleukin‐1 receptor (IL‐1R)

signaling in immune cells including B lymphocytes. It forms the Myd-

dosome complex with the myeloid differentiation primary response

88 (MYD88) adaptor protein, driving maximal activation of Nuclear

Factor Kappa B (NFkB) causing inﬂammatory and immune responses

and tumor promotion. Preclinical studies demonstrated the role of

IRAK4 activation as a driver of secondary, adaptive tumor resistance

and tumor survival mechanisms that could be delayed or reversed. CA‐

4948 is a novel small molecule, oral inhibitor of IRAK4. When com-

bined with the Bruton kinase (BTK) inhibitors, it has shown in‐vivo

synergy in B‐cell Non‐Hodgkin Lymphoma (NHL) models. CA‐4948

was previously reported to be well tolerated and active as mono-

therapy in heavily pretreated relapsed / refractory NHL.

Methods: An ongoing trial of CA‐4948 in combination with ibrutinib

in relapsed or refractory hematologic malignancies (NCT03328078).

Rationale: Demonstration of synergy between CA‐4948 and ibruti-

nib. The study is designed as follows:

Part A: Dose escalation monotherapy, results from the phase 1 study

were presented at American Society of Hematology (ASH) 2020.

Part A2 Combination: Dose escalation with a 3 +3 design. Primary

objectives: Safety/tolerance, maximum tolerated dose (MTD), rec-

ommended phase 2 dose (RP2D). Secondary objectives: pharmaco-

kinetics (PK) and preliminary efﬁcacy. Exploratory objectives:

Correlation with MYD88‐L265P mutation status

Part B Combination: A basket design of 4 expansion cohorts with a

Simon 2‐Stage approach, applied to each cohort.

Primary objective: Efﬁcacy; complete response (CR), objective

response rate (ORR) and duration of response (DOR). Secondary

objectives:Safety and tolerance, progression free survival (PFS) and

population‐PK. Exploratory objective: biomarkers correlations.

Inclusion criteria for Part A2, NHL subtypes (WHO 2016):

Follicular lymphoma, marginal zone lymphoma (MZL), mantle cell

lymphoma (MCL), diffused large B‐cell lymphoma (DLBCL), chronic

lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma

(SLL), primary or secondary central nervous system lymphoma (CNS),

Waldenström macroglobulinemia (WM) and lymphoplasmacytic

lymphoma (LPL). Part B: cohorts 1‐3 include BTK‐inhibitor naïve

patients of similar histologies to part A2, cohort 4 includes patients

with adaptive ibrutinib resistance.

Exclusions for both Parts A2 and B: Signiﬁcant acute or chronic un-

resolved toxicity from prior therapy; serious co‐morbidities.

Summary: CA‐4948 is a novel oral IRAK4 inhibitor of the TLR/

myddosome pathway that showed preclinical synergistic activity in

combination with ibrutinib. Clinical safety, tolerance, and preliminary

efﬁcacy in selected NHL cohorts are being studied.

Keywords: Ongoing Trials

No conﬂicts of interests pertinent to the abstract.

258 |EPSTEIN‐BARR VIRUS‐DRIVEN DISEASES: A

MULTINATIONAL, MULTICOHORT, OPEN‐LABEL PHASE 2 STUDY

TO ASSESS THE EFFICACY AND SAFETY OF TABELECLEUCEL

USING AN ADAPTIVE STUDY DESIGN

S. Choquet

, J. A. Pérez‐Simón

, N. Worel

, S. Chaganti

, R. Dinavahi

N. Guzman‐Becerra

, W. Navarro

, Y. Sun

, L. Gamelin

Hôpital Pitié‐Salpêtrière, Hématologie, Paris, France,

Hospital

Universitario Virgen del Rocío, Hematología, Sevilla, Spain,

Medical

University of Vienna, Blutgruppenserologie and Transfusionsmedizin,

Vienna, Austria,

Queen Elizabeth Hospital Birmingham, Hematology,

Birmingham, UK,

Atara Biotherapeutics, Clinical Sciences, South San

Francisco, USA,

Atara Biotherapeutics, Biostatistics, Thousand Oaks,

USA,

Atara Biotherapeutics, Drug Safety and Pharmacovigilance, South

San Francisco, USA

Introduction: Epstein–Barr virus (EBV) infection is associated with a

variety of life‐threatening malignant and non‐malignant diseases. In

immunocompromised individuals, impaired immunosurveillance can

result in uncontrolled EBV infection. This may lead to EBV

348

SUPPLEMENT ABSTRACTS

immunodeﬁciency‐associated lymphoproliferative disorders (AI‐

LPD), EBV

sarcomas, or EBV‐associated end‐organ damage. EBV‐

driven LPDs are a heterogeneous group of diseases with variable

clinical and pathologic features, including primary IA‐LPD (EBV

PID‐

LPD), acquired IA‐LPD (EBV

AID‐LPD) often associated with HIV

infection, and post‐transplant lymphoproliferative disorder (EBV

PTLD). In addition, EBV infection of mesenchymal cells can cause

sarcomas, including leiomyosarcoma (EBV

sarcoma). In rare in-

stances, EBV viremia (ie persistent EBV infection) is associated with

life‐threatening complications such as chronic active EBV (CAEBV)

and hemophagocytic lymphohistiocytosis (HLH).

Tabelecleucel is an investigational, off‐the‐shelf, allogeneic T‐cell

immunotherapy without genetic modiﬁcation. Initial safety and efﬁ-

cacy data showed that tabelecleucel was well tolerated and displayed

clinical activity in patients with each of the EBV‐driven diseases

being proposed in this study (ATA129‐EBV‐205; Kurlander et al. Ann

Oncol 2018; Nikiforow et al. Blood 2020; Torno et al. Blood 2020;

Prockop et al. J Clin Invest 2020). A Phase III study of tabelecleucel

for solid‐organ or allogeneic hematopoietic cell transplant patients

with EBV

PTLD after failure of rituximab or rituximab plus

chemotherapy (NCT03394365) is ongoing.

Methods: This is a multinational, multicohort, open‐label, single arm

per cohort, Phase II study to assess the efﬁcacy and safety of tabe-

lecleucel in patients with EBV‐associated diseases (ATA129‐EBV‐

205; NCT04554914). Participants with Epstein‐Barr virus (EBV)‐

driven diseases where standard ﬁrst‐line therapy is not appropriate

or who are relapsed/refractory to standard ﬁrst‐line therapy will be

enrolled in the following cohorts: EBV+AID‐LPD, EBV+PID‐LPD,

EBV+sarcoma (including leiomyosarcoma [LMS]), CAEBV/HLH,

EBV +PTLD with central nervous system (CNS) involvement and

ﬁrst‐line inappropriate EBV+PTLD. Prior to screening, the avail-

ability of tabelecleucel from an existing inventory based on an

appropriate HLA restriction and allele proﬁle will be conﬁrmed.

Tabelecleucel will be administered in cycles lasting 35 days. At the

end of each cycle, responses will be assessed per disease‐speciﬁc

criteria. An adaptive two‐stage design will be used for each cohort

in this study, and for each, a maximum of 8 patients will be enrolled in

stage 1. The decision to move to stage 2 enrollment for any given

cohort will be based on an analysis of the ﬁrst 8 evaluable patients in

the cohort using investigator's assessment (per disease‐speciﬁc

response criteria).

The research was funded by: Atara Biotherapeutics.

Keywords: Ongoing Trials

Conﬂicts of interests pertinent to the abstract

S. Choquet

Consultant or advisory role: Atara Biotherapeutics

J. A. Pérez‐Simón

Honoraria: Atara Biotherapeutics

S. Chaganti

Consultant or advisory role: Atara Biotherapeutics

R. Dinavahi

Employment or leadership position: Atara Biotherapeutics

Stock ownership: Atara Biotherapeutics

N. Guzman‐Becerra

Employment or leadership position: Atara Biotherapeutics

Stock ownership: Atara Biotherapeutics

W. Navarro

Employment or leadership position: Atara Biotherapeutics

Stock ownership: Atara Biotherapeutics

Y. Sun

Employment or leadership position: Atara Biotherapeutics

Stock ownership: Atara Biotherapeutics

L. Gamelin

Employment or leadership position: Atara Biotherapeutics

Stock ownership: Atara Biotherapeutics

259 |A PHASE II STUDY OF ACALABRUTINIB IN

COMBINATION WITH R‐CHOP CHEMOTHERAPY PRIOR TO

AUTOLOGOUS STEM CELL TRANSPLANTATION IN PREVIOUSLY

UNTREATED MANTLE CELL LYMPHOMA

D. Villa

, D. W. Scott

, R. Morin

, H. Nakamura

, J. F. Larouche

, M.

Cheung

, N. Johnson

, M. Elemary

, M. M. Keating

, P. Tonseth

, K.

Zukotynski

, S. Mayo

, R. Goswami

, R. Laister

, J. Kuruvilla

BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,

Centre

Hospitalier Universitaire de Québec, Hôpital de l’Enfant‐Jésus, Quebec

City, Canada,

Sunnybrook Health Sciences Centre, Department of

Hematology, Toronto, Canada,

Jewish General Hospital, Department of

Hematology, Montreal, Canada,

Saskatchewan Cancer Agency,

Saskatoon Cancer Centre, Saskatoon, Canada,

Nova Scotia Cancer

Centre, QEII Health Sciences Centre, Halifax, Canada,

BC Cancer,

Department of Functional Imaging, Vancouver, Canada,

McMaster

University, Departments of Radiology and Medicine, Hamilton, Canada,

University of Toronto, Lawrence S. Bloomberg Faculty of Nursing,

Toronto, Canada,

Sunnybrook Health Sciences Centre, Department of

Laboratory Medicine and Pathobiology, Toronto, Canada,

University

Health Network, Princess Margaret Cancer Centre, Toronto, Canada

Introduction: Rituximab in combination with cytotoxic chemotherapy

followed by autologous stem cell transplantation (ASCT) and main-

tenance rituximab (MR) is a standard treatment strategy in young

and ﬁt patients with mantle cell lymphoma (MCL). Various chemo-

therapy regimens can be used as part of induction therapy, but there

is no single standard of care.

Frontline therapy can be improved by adding novel agents such

as Bruton tyrosine kinase inhibitors (BTKi) which are active in

relapsed/refractory MCL and can be safely combined with immu-

nochemotherapy. In the European Triangle study (NCT02858258)

ibrutinib is given for 3 weeks with R‐CHOP, but not with R‐DHAP,

SUPPLEMENT ABSTRACTS

349

which means patients receive intermittent BTKi exposure before

ASCT. Continuous, uninterrupted BTKi could maximize the beneﬁt of

front‐line therapy given that responses are known to develop over

time.

Acalabrutinib achieves BTK inhibition at lower doses than ibruti-

nib and also has less off‐target BTK inhibition. We hypothesize that

combining continuous acalabrutinib with R‐CHOP may result in a

tolerable, outpatient, highly active regimen allowing a high proportion

of patients to proceed with ASCT and/or achieve MRD negativity.

Methods: NCT04566887 is a phase II, non‐randomized, open‐label,

single‐arm study conducted across 7 academic centres in Canada.

Patients ≥18 years of age with previously untreated MCL, perfor-

mance status 0‐2, adequate organ function and considered ﬁt for

ASCT will be included.

Patients receive 6 cycles of R‐CHOP at standard doses plus aca-

labrutinib 100 mg twice per day orally (Figure 1). Responding patients

proceed with ASCT and subsequently receive MR and acalabrutinib for

a total of 2 years. Patients who do not proceed to ASCT for reasons

other than progressive disease also receive MR and acalabrutinib.

The primary endpoint is the complete response rate after 6 cy-

cles of induction with centrally reviewed PET/CT using the Lugano

Classiﬁcation for Malignant Lymphoma. Secondary endpoints include

frequency of adverse events, response rates according to the Inter-

national Working Group consensus response evaluation criteria in

lymphoma (RECIL 2017), rate of minimal residual disease (MRD)

negativity prior to ASCT and at any time during study treatment,

event‐free survival, and overall survival.

MRD testing will be performed on serial peripheral blood and

bone marrow aspirates using a panel that covers commonly mutated

MCL genes, including the CCND1 breakpoint region. Serial peripheral

blood samples will also be used for other correlative studies including

analyses of circulating tumor DNA and microRNA. Diagnostic tumor

tissue will be centrally analyzed using the MCL35 assay. Patient re-

ported outcomes will be assessed using the FACT‐Lym and EORTC

QLQ‐C30 questionnaires.

The sample size is n =54. The ﬁrst patient was enrolled in March

2021. Accrual is expected to continue for 2‐3 years.

Keywords: Molecular Targeted Therapies, Indolent non‐Hodgkin

lymphoma, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

D. Villa

Consultant or advisory role: Janssen, Nanostring

Research funding: AstraZeneca (research funding to the institution)

J. Kuruvilla

Research funding: AstraZeneca (research funding to the institution)

260 |FIRST‐LINE IBRUTINIB +VENETOCLAX TREATMENT FOR

MANTLE CELL LYMPHOMA IN OLDER PATIENTS OR THOSE

WITH TP53 MUTATION: A NEW OPEN‐LABEL ARM OF THE

PHASE 3 PCYC‐1143 SYMPATICO STUDY

W. Jurczak

, C. Tam

, K. Eckert

, J. Lin

, J. K. Neuenburg

, M. L.

Wang

Maria Sklodowska‐Curie National Institute of Oncology, Department of

Clinical Oncology, Kraków, Poland,

Peter MacCallum Cancer Centre & St.

Vincent's Hospital, Department of Haematology, Melbourne, Australia,

Pharmacyclics LLC, an AbbVie Company, Oncology Division, Sunnyvale,

California, USA,

Pharmacyclics LLC, an AbbVie Company, Department of

Biostatistics, Sunnyvale, California, USA,

MD Anderson Cancer Center,

Department of Lymphoma – Myeloma, Houston, Texas, USA

Introduction: Ibrutinib is a once‐daily Bruton tyrosine kinase (BTK)

inhibitor approved in the US for patients with mantle cell lymphoma

(MCL) who have received ≥1 prior therapy. Having demonstrated

overall response rates of 68–72% and complete response (CR) rates

of 19–21%, single‐agent ibrutinib received accelerated US approval

for MCL (Wang NEJM 2013; Dreyling Lancet 2016). Venetoclax, a B‐

cell lymphoma 2 (BCL2) inhibitor, is approved in the US for patients

with previously untreated acute myeloid leukemia and for patients

with CLL who received ≥1 prior therapy. Single‐agent venetoclax

demonstrated a CR rate of 21% in patients with MCL (Davids J Clin

Oncol 2017). In preclinical models, dual inhibition of BTK pathways by

ibrutinib and BCL2 pathways by venetoclax resulted in synergistic

antitumor activity (Zhao Br J Haematol 2015). In the phase 2 AIM

study conducted in patients with MCL, combination treatment with

ibrutinib plus venetoclax resulted in a best response of CR in 71% of

24 patients. Importantly, in patients with a TP53 mutation, who are

considered chemo‐insensitive, the CR rate was 50%, including one

previously untreated patient (Tam NEJM 2018). The objective of this

new, open‐label arm of the ongoing phase 3 SYMPATICO study is to

evaluate ﬁrst‐line ibrutinib plus venetoclax in patients ≥65 years and

in patients <65 years with a TP53 mutation, populations that have an

unmet need for chemotherapy‐free regimens and for whom limited

treatment options exist.

Methods: Approximately 75 patients with MCL will be enrolled in

this new open‐label arm of the ongoing phase 3 SYMPATICO trial.

Eligibility criteria include patients with pathologically conﬁrmed,

previously untreated MCL who are either ≥65 years or 18–64 years

with a TP53 mutation. All patients must have measurable disease

and an Eastern Cooperative Oncology Group performance status of

0–2. Patients will be ineligible if they have received prior treatment

with a BTK or BCL2 inhibitor or have blastoid‐variant MCL or a

history or current evidence of CNS lymphoma. Patients will receive

350

SUPPLEMENT ABSTRACTS

oral, once‐daily ibrutinib 560 mg plus venetoclax in a 5‐week ramp‐

up to 400 mg. Treatment will continue for up to 24 months, after

which venetoclax will be discontinued in all patients and single‐

agent ibrutinib will continue until progressive disease or unaccept-

able toxicity. The primary objective is to evaluate the CR rate;

secondary objectives include additional efﬁcacy evaluations, safety,

and pharmacokinetics. Status: The new arm of the SYMPATICO

study conducted in previously untreated patients is currently

enrolling at multiple global sites; anticipated completion is in 2022.

As of Jan 11, 2021, the study is recruiting only those patients with

known TP53 mutations, including those aged 65 and older, for

enrollment.

EA – previously submitted to regional or national meetings (up to

1000 attendees).

The research was funded by: Pharmacyclics LLC, an AbbVie Company

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Immuno-

therapy, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

W. Jurczak

Consultant or advisory role: Acerta, Astra Zeneca, BeiGene, Epizyme,

Janssen, Loxo, Novartis, and Sandoz

Research funding: Acerta, Bayer, BeiGene, Janssen, MeiPharma,

Merck, Pharmacyclics LLC, an AbbVie Company, Roche, Takeda, and

TG Therapeutics

C. Tam

Consultant or advisory role: AbbVie, BeiGene, Janssen, Loxo

Oncology, and Roche

Honoraria: AbbVie, BeiGene, Janssen, Novartis, and Pharmacyclics

LLC, an AbbVie Company

Research funding: AbbVie and Janssen

K. Eckert

Employment or leadership position: Pharmacyclics LLC, an AbbVie

Company

Stock ownership: AbbVie

J. Lin

Employment or leadership position: Pharmacyclics LLC, an AbbVie

Company

Stock ownership: AbbVie

J. K. Neuenburg

Employment or leadership position: Pharmacyclics LLC, an AbbVie

Company

Stock ownership: AbbVie

M. L. Wang

Consultant or advisory role: AstraZeneca, Celgene, Guidepoint

Global, InnoCare, Janssen, Juno, Kite Pharma, Loxo Oncology, Mor-

eHealth, Nobel Insights, Oncternal, Pharmacyclics LLC, an AbbVie

Company, and Pulse Biosciences

Honoraria: AstraZeneca, Beijing Medical Award Foundation, Dava

Oncology, Janssen, Lu Daopei Medical Group, OMI, OncLive, Phar-

macyclics LLC, an AbbVie Company, and Targeted Oncology

Research funding: Acerta Pharma, AstraZeneca, BioInvent, Celgene,

Janssen, Juno Therapeutics, Kite Pharma, Loxo Oncology, Molecular

Templates, Oncternal, Pharmacyclics LLC, an AbbVie Company,

VelosBio, and Verastem

Educational grants: Acerta, AstraZeneca, BioInvent, Celgene, Jans-

sen, Juno Therapeutics, Kite Pharma, Loxo Oncology, Molecular

Templates, Oncternal, Pharmacyclics LLC, an AbbVie Company,

VelosBios, and Verastem

261 |THREE PHASE 1/2, OPEN‐LABEL STUDIES OF CEREBLON

E3 LIGASE MODULATOR (CELMOD)‐BASED REGIMENS IN

NEWLY DIAGNOSED (ND) OR RELAPSED/REFRACTORY (R/R)

NON‐HODGKIN LYMPHOMA (NHL)

F. Morschhauser

, G. S. Nowakowski

, G. Cartron

, V. Kesanakurthy

A. Gkasiamis

, P. Patah

, R. Delarue

, T. Wang

, J. Li

, D. Xian

, C. P.

Fox

, P. Martin

Université de Lille, Centre Hospitalier Universitaire de Lille. ULR 7365,

GRITA – Groupe de Recherche sur les formes Injectables et les

Technologies Associées, Département d'Hématologie, Lille, France,

Mayo Clinic Hospital, Department of Hematology, Rochester,

Minnesota, USA,

CHU de Montpellier – Hôpital Saint‐Eloi, Départe-

ment d'Hématologie clinique, Montpellier, France,

Bristol Myers

Squibb, Global Drug Development, Princeton, New Jersey, USA,

Bristol

Myers Squibb, Global Drug Development, Neuchâtel, Switzerland,

Bristol Myers Squibb, Global Drug Development, Princeton, New Jer-

sey, USA,

Bristol Myers Squibb, Global Drug Development, Neuchâtel,

Switzerland,

Bristol Myers Squibb, Global Biometrics and Data Sci-

ences, Princeton, New Jersey, USA,

Bristol Myers Squibb, Global Bio-

metrics and Data Sciences, Princeton, New Jersey, USA,

Bristol Myers

Squibb, Global Biometrics and Data Sciences, Princeton, New Jersey,

USA,

Nottingham University Hospitals NHS Trust, Department of

Clinical Haematology, Nottingham, UK,

Weill Cornell Medicine, Divi-

sion of Hematology/Oncology, New York, New York, USA

Introduction: Lenalidomide (LEN)‐based therapies have shown ac-

tivity in NHL. These include LEN +anti‐CD20 agent (rituximab or

obinutuzumab) in follicular lymphoma (Morschhauser et al. N Engl J

Med 2018; Morschhauser et al. Lancet Haematol 2019) and in R/R

NHL (Wang et al. Leukemia 2013), as well as LEN +tafasitamab in R/R

diffuse large B‐cell lymphoma (DLBCL; Salles et al. Lancet Oncol

2020). Additionally, LEN +R‐CHOP demonstrated signiﬁcantly

improved progression‐free survival (PFS) versus R‐CHOP in ND

DLBCL (Nowakowski, Hong et al. J Clin Oncol 2021), and a positive

trend in PFS in ABC subtype of ND DLBCL (Nowakowski, Chiappella

et al. J Clin Oncol 2021). Early results also showed clinical activity of

LEN +polatuzumab vedotin/obinutuzumab in R/R follicular lym-

phoma (Diefenbach et al. ASH 2019). Iberdomide (IBER; CC‐220) and

CC‐99282 are novel oral CELMoDs that induce degradation of

SUPPLEMENT ABSTRACTS

351

Ikaros/Aiolos, resulting in immunomodulatory and antitumor effects.

IBER has 20x higher cereblon‐binding afﬁnity than LEN, leading to

signiﬁcantly faster degradation of target substrates (Matyskiela et al.

J Med Chem 2018), and is active in NHL cell lines. CC‐99282 displays

efﬁcacy in DLBCL cell lines independent of cell of origin. Thus, the

use of CELMoDs may provide more effective therapies for ND and R/

R NHL. Here we describe 3 dose‐ﬁnding and safety studies (1 for

NHL, 2 for aggressive B‐cell lymphoma [a‐BCL]) that will assess

CELMoDs in combination with anti‐CD20 agents, R‐CHOP, or other

agents in NHL.

352

SUPPLEMENT ABSTRACTS

Methods: CC‐220‐NHL‐001, CC‐220‐DLBCL‐001, and CC‐220‐

DLBCL‐002 are phase 1/2, open‐label, multicenter, dose‐escalation

(part 1) and dose‐expansion (part 2) studies. Eligible patients (pts)

aged ≥18 years must have ND a‐BCL (Study DLBCL‐001), or R/R

lymphoma (Study NHL‐001) or R/R a‐BCL (Study DLBCL‐002) with ≥

2 prior lines of therapy, as well as measurable disease per Lugano

2014 classiﬁcation, and ECOG performance status of 0–2. Primary

objectives are to determine the maximum tolerated dose and rec-

ommended phase 2 dose (RP2D) of IBER (all studies) or CC‐99282

(Study DLBCL‐001 only), as well as to evaluate safety/tolerability

at RP2D (Study DLBCL‐001 only) and efﬁcacy (Study DLBCL‐002

only). Secondary objectives include safety, pharmacokinetics, and

efﬁcacy. In Study NHL‐001, pts will be enrolled in treatment (tx)

cohorts based on lymphoma subtype (Figure). In part 1 of each study,

pts will receive the assigned tx, including IBER or CC‐99282 at

escalating dose levels; in part 2, pts will receive CELMoD‐based tx at

the RP2D determined in part 1 (Figure). All tx will continue until the

planned number of cycles is reached or progression/unacceptable

toxicity.

EA – previously submitted to ASCO 2021.

The research was funded by: Bristol Myers Squibb

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Indolentnon‐

Hodgkin lymphoma, OngoingTrials

Conﬂicts of interests pertinent to the abstract

F. Morschhauser

Consultant or advisory role: Roche, Genentech, Servier

Other remuneration: Speakers' bureau: Roche, Gilead, Janssen.

Board of directors or advisory committee: Roche, Gilead, Abbvie,

Celgene, Epizyme

G. Cartron

Consultant or advisory role: Roche, Celgene

Honoraria: Jansen, Sanoﬁ, Novartis, Gilead, Roche, Celgene

V. Kesanakurthy

Employment or leadership position: Bristol Myers Squibb

A. Gkasiamis

Employment or leadership position: Bristol Myers Squibb

P. Patah

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

R. Delarue

Employment or leadership position: Celgene, a Bristol Myers Squibb

company

Stock ownership: Bristol Myers Squibb

T. Wang

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb, Vir Biotechnology

J. Li

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

Educational grants: Bristol Myers Squibb

D. Xian

Employment or leadership position: Bristol Myers Squibb

C. P. Fox

Consultant or advisory role: Abbvie, AstraZeneca, Atarabio, Bristol

Myers Squibb/Celgene, Gilead, Janssen, Incyte, Roche, Takeda

Honoraria: Abbvie, Atarabio, Bristol Myers Squibb/Celgene, Janssen,

Incyte, Roche, Takeda

Research funding: Abbvie, Gilead, Roche, Takeda

Educational grants: Abbvie, Bristol Myers Squibb/Celgene, Janssen,

Roche, Takeda

P. Martin

Consultant or advisory role: ADCT, AstraZeneca, Bayer, BeiGene,

Bristol Myers Squibb, Cellectar, Epizyme, Gilead, Incyte, Janssen,

Karyopharm, Merck, Regeneron, Takeda, Teneobio, Verastem

262 |COASTAL: A PHASE 3 STUDY OF THE PI3KδINHIBITOR

ZANDELISIB WITH RITUXIMAB (R) VERSUS

IMMUNOCHEMOTHERAPY IN PATIENTS WITH RELAPSED

INDOLENT NON‐HODGKIN'S LYMPHOMA (INHL)

W. Jurczak

, P. L. Zinzani

, D. Cunningham

, S. Yavrom

, W. Huang

, I.

Gorbatchevsky

, V. Ribrag

Maria Sklodowska‐Curie National Research Institute of Oncology, He-

matology, Krakow, Poland,

Institute of Hematology "L. e A. Seràgnoli",

Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Bologna,

Italy,

Royal Marsden Hospital, NHS Foundation Trust, Haematology‐

Oncology, London, UK,

MEI Pharma Inc., Clinical Development, San

Diego, USA,

MEI Pharma Inc., Biostats, San Diego, USA,

MEI Pharma

Inc., Clinical Development, San Diego, USA,

Institut Gustave Roussy,

Hematology, Villejuif, France

Background: Patients (pts) with iNHL treated with front‐line immu-

nochemotherapy may beneﬁt from an alternative, chemotherapy‐

free regimen at relapse. Zandelisib, a potent, selective, and struc-

turally differentiated oral PI3Kδinhibitor, achieved an 87% response

rate, with median duration of response not reached in iNHL when

given as a monotherapy or in combination with R. A low rate (<10%)

of Grade ≥3 immune‐mediated adverse events of special interest

associated with PI3kδinhibitors is observed in patients administered

zandelisib on an intermittent schedule (IS) (JCO 2020 38:15_suppl,

8016). An open‐label, phase 2 study (TIDAL, NCT03768505) of

zandelisib as monotherapy is ongoing in pts with relapsed/refractory

follicular lymphoma (FL) and marginal zone lymphoma (MZL).

Methods: The COASTAL study is a randomized, open‐label,

controlled multicenter phase 3 trial to investigate the safety and

efﬁcacy of zandelisib in combination with R versus standard

SUPPLEMENT ABSTRACTS

353

immunochemotherapy in pts with iNHL. Key eligibility criteria: adults

with relapsed or refractory FL or MZL who received ≥1 prior lines of

therapy which must have included an anti‐CD20 antibody in combi-

nation with chemotherapy or lenalidomide (L); at least one bi‐

dimensionally measured lesion >1.5 cm; adequate bone marrow,

renal and hepatic function; ECOG performance status score of 0 to 1.

Key exclusion criteria: histologically conﬁrmed diagnosis of FL grade

3b or transformed disease; administration of 2 prior immunoche-

motherapy regimens; prior PI3K inhibitor therapy; known lympho-

matous involvement of the central nervous system. Subjects will be

randomized 1:1 to receive R‐zandelisib or immunochemotherapy (R‐

CHOP or R‐B) and stratiﬁed by type and number of prior treatment

regimens, histology, and duration of treatment‐free interval after last

therapy. Zandelisib will be given in a 28‐day cycle comprising of daily

dosing for 2 cycles followed by IS dosing on days 1‐7 or each 28‐day

subsequent cycle for a duration of 2 years. Rituximab or immu-

nochemotherapy will be given for a total of 6 cycles. Disease

response will be assessed by an Independent Response Review

Committee according to the modiﬁed Lugano Classiﬁcation. Radio-

graphic tumor assessment will be performed approximately every 12

weeks for the ﬁrst 9 months, every 16 weeks for the next 12 months,

and every 24 weeks thereafter. The primary efﬁcacy endpoint is

progression‐free survival. The major secondary endpoints include

ORR, complete response rate, overall survival, and safety. The trial

will enroll approximately 534 pts in ∼200 sites globally and will begin

enrollment in mid‐2021 (NCT04745832).

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: MEI Pharma Inc.

Keywords: Indolent non‐Hodgkin lymphoma, Molecular Targeted

Therapies, Ongoing Trials

No conﬂicts of interests pertinent to the abstract.

263 |INMIND: A PHASE 3 STUDY OF TAFASITAMAB +

LENALIDOMIDE AND RITUXIMAB VS PLACEBO +

LENALIDOMIDE AND RITUXIMAB FOR RELAPSED/REFRACTORY

FOLLICULAR OR MARGINAL ZONE LYMPHOMA

K. Hübel

, C. W. Scholz

, S. Luminari

, A. Salar

, B. E. Wahlin

, A. K.

Gopal

, C. Bonnet

, M. Trneny

, S. Paneesha

, O. Manzke

, F.

Seguy

, D. Li

, L. H. Sehn

University Hospital Cologne, Department of Internal Medicine I Oncology

and Hematology, Cologne, Germany,

Vivantes Klinikum Am Urban,

Department of Hematology and Oncology, Berlin, Germany,

Azienda

USL‐IRCCS di Reggio Emilia, Hematology Unit, Reggio Emilia, Italy,

Hospital del Mar‐IMIM, Department of Haematology, Barcelona, Spain,

Unit of Hematology, Karolinska Institute, Department of Medicine,

Stockholm, Sweden,

University of Washington Medicine, Division of

Medical Oncology, Seattle, Washington, USA,

Centre Hospitalier Uni-

versitaire, University of Liège, Clinical Hematology, Liège, Belgium,

First

Faculty of Medicine, Charles University, General Hospital, First Depart-

ment of Medicine, Prague, Czech Republic,

University Hospitals

Birmingham NHS Foundation Trust, Hematology, Birmingham, UK,

Incyte Biosciences International Sàrl, Clinical Development, Morgues,

Switzerland,

Incyte Corporation, Biostatistics, Wilmington, Delaware,

USA,

BC Cancer Centre for Lymphoid Cancer and The University of

British Columbia, Division of Medical Oncology, Vancouver, Canada

Background: Most patients (pts) with the indolent non‐Hodgkin

lymphoma (NHL) subtypes follicular lymphoma (FL) or marginal

zone lymphoma (MZL) respond to ﬁrst‐line treatment but relapse is

common, and there is no single standard treatment for pts with

relapsed/refractory (R/R) FL or MZL. Tafasitamab is an Fc‐

engineered humanized monoclonal antibody (mAb) against CD19

which is broadly expressed in FL and MZL, and regulates B‐cell

proliferation via B‐cell receptor signaling. In preclinical studies,

tafasitamab has shown activity against NHL cell lines in combination

with rituximab (anti‐CD20 mAb) and lenalidomide (LEN). Tafasitamab

monotherapy has shown promising clinical activity in a phase 2a

study in pts with R/R NHL (NCT01685008), with an ORR of 29% (n/N

=10/34) in pts with FL and 33% (n/N =3/9) in pts with MZL. In an

ongoing phase 2, single‐arm study (L‐MIND, NCT02399085), tafasi-

tamab plus LEN followed by tafasitamab alone demonstrated an ORR

of 57.5% (n/N =46/80), CR of 40% (n/N =32/80) and median DOR

of 34.6 months (95% CI: 26.1–NR), in pts with R/R diffuse large B‐cell

lymphoma (FDA approved indication). These preclinical and clinical

observations from phase 2 trials suggest a potential clinical beneﬁt of

tafasitamab plus LEN and rituximab for pts with R/R FL or MZL.

Methods: This phase 3 double‐blind, placebo‐controlled, randomized

study is designed to investigate whether tafasitamab plus LEN and

rituximab provides improved clinical beneﬁt compared with LEN and

rituximab in pts with R/R FL or R/R MZL. Pts will be randomized 1:1

to receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28‐

day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) plus LEN (20

mg PO QD [10 mg PO QD if creatinine clearance ≥30 to <60 mL/

minute], days 1–21/ cycle for 12 cycles) and rituximab (375 mg/m

on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or

placebo (0.9% saline solution IV) plus LEN and rituximab. The primary

study endpoint is PFS (investigator assessed [INV] by Lugano 2014

criteria) for pts with FL. Key secondary endpoints are PFS (INV) in

overall population (FL and MZL), PET‐CR rate (INV) at end of

treatment (4–8 weeks after last treatment) and OS in pts with FL.

Inclusion criteria include age ≥18 y, histologically conﬁrmed FL

(grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented

R/R disease, ≥1 prior systemic anti‐CD20 therapy (including anti‐

CD20 refractory disease), ECOG PS ≤2, adequate systemic organ

function, and high tumor burden (per GELF criteria). Exclusion

criteria include prior rituximab plus LEN treatment, history of

radiotherapy for other diseases (≥25% of bone marrow), non-

hematologic malignancy, congestive heart failure (LVEF <50%),

active systemic infection, known CNS lymphoma, or severe immu-

nocompromised state. inMIND (NCT04680052, EudraCT2020‐

004407‐13) is currently enrolling pts; planned enrollment is 528 pts

with R/R FL and 60–90 pts with R/R MZL.

EA – previously submitted to ASCO and EHA 2021.

354

SUPPLEMENT ABSTRACTS

The research was funded by: Incyte Corporation

Keywords: Indolent non‐Hodgkin lymphoma, Combination Therapies,

Ongoing Trials

Conﬂicts of interests pertinent to the abstract

K. Hübel

Consultant or advisory role: Celgene, EUSA, Gilead, Incyte, Roche,

Servier

C. W. Scholz

Consultant or advisory role: Roche

S. Luminari

Consultant or advisory role: Bristol Myers Squibb, Genmab, Jannsen,

Regeneron, Roche

A. Salar

Consultant or advisory role: Celgene, Janssen, and Roche

Research funding: Gilead

B. E. Wahlin

Consultant or advisory role: Roche

Research funding: Gilead

A. K. Gopal

Honoraria: Incyte, MorphoSys

C. Bonnet

Consultant or advisory role: Roche

M. Trneny

Consultant or advisory role: AbbVie, Amgen, Bristol‐Myers Squibb,

Celgene, Gilead Sciences, Incyte, Janssen, MorphoSys, Roche, Takeda

Honoraria: AbbVie, Amgen, Bristol‐Myers Squibb, Gilead Sciences,

Incyte, Janssen, MorphoSys, Roche, Takeda

Other remuneration: AbbVie, Bristol‐Myers Squibb, Gilead Sciences,

Janssen, Roche, Takeda

S. Paneesha

Honoraria: Celgene, Roche

O. Manzke

Employment or leadership position: Incyte

Stock ownership: Incyte

F. Seguy

Employment or leadership position: Incyte

Stock ownership: Incyte

D. Li

Employment or leadership position: Incyte

Stock ownership: Incyte

L. H. Sehn

Consultant or advisory role: AbbVie, Acerta, Apobiologix, AstraZe-

neca, Celgene, Debiopharm, Genentech, Genmab, Gilead, Incyte,

Janssen, Karyopharm, Kite, Lundbeck, Merck, MorphoSys, Novartis,

Sandoz, Takeda, TG Therapeutics, Verastem, Roche, Seattle Genetics,

Teva

Research funding: Teva

264 |A PHASE 2 RANDOMIZED STUDY OF LONCASTUXIMAB

TESIRINE (LONCA) VERSUS (VS) IDELALISIB IN PATIENTS (PTS)

WITH RELAPSED OR REFRACTORY (R/R) FOLLICULAR

LYMPHOMA (FL) – LOTIS‐6

C. Carlo‐Stella

, J. Depaus

, B. T. Hess

, E. Kingsley

, P. L. Zinzani

, D.

Ungar

, V. Dai

, L. Wang

, K. M. Ardeshna

Humanitas Clinical and Research Center – IRCCS, and Humanitas

University, Department of Oncology and Hematology, Rozzano, Milan,

Italy,

CHU UCL Namur site Godinne, Department of Hematology, Yvoir,

Belgium,

Medical University of South Carolina, Division of Hematology

and Medical Oncology, Department of Medicine, Charleston, USA,

Comprehensive Cancer Centers of Nevada, Las Vegas, USA,

IRCCS

Azienda Ospedaliero‐Universitaria di Bologna Istituto di Ematologia

"Seràgnoli" and Diagnostica e Sperimentale Università di Bologna,

Dipartimento di Medicina Specialistica, Bologna, Italy,

ADC Therapeutics

America, Inc, Clinical Development, Murray Hill, USA,

University College

London Hospitals NHS Foundation Trust, Department of Haematology,

London, UK

Introduction: Many pts with FL respond to ﬁrst‐line therapy, but

most have successive relapses and response duration shortens

after each relapse; FL is hence an area of substantial unmet

need. Single‐agent Lonca, an antibody (Ab)‐drug conjugate

comprising a humanized anti‐CD19 monoclonal Ab conjugated to a

pyrrolobenzodiazepine dimer (PBD) toxin, showed antitumor ac-

tivity and manageable safety in R/R B‐cell non‐Hodgkin lymphoma

eg, FL in a Phase 1 trial (ADCT‐402‐101) and in heavily pretreated

pts with R/R diffuse large B‐cell lymphoma in a Phase 2 trial

(ADCT‐402‐201). Idelalisib is a phosphatidylinositol 3‐kinase in-

hibitor approved for pts with relapsed FL with ≥2 prior systemic

therapies.

The primary objective of this trial (NCT04699461; opened

in Spring 2021) is to assess the efﬁcacy of Lonca vs idelalisib in

R/R FL.

Methods: Key inclusion criteria in the prospective, randomized, 2‐

arm, multicenter, open‐label, Phase 2 trial include: age ≥18 years;

pathologic FL diagnosis (Grade 1, 2, 3A); ≥2 prior therapy lines (≥1 of

which included an anti‐CD20 therapy); measurable disease as deﬁned

by the 2014 Lugano Classiﬁcation; and adequate organ function and

performance status. Pts will be randomized 2:1 to Lonca (intrave-

nously; 150 µg/kg every 3 weeks [Q3W] for 2 cycles then 75 µg/kg

Q3W for subsequent cycles) or idelalisib (oral; 150 mg twice daily),

based on time since last systemic therapy (ie, ≤2 years vs >2 years).

The follow‐up period will be ≤3 years after treatment end. Pts can

continue therapy until disease progression, unacceptable toxicity, or

other discontinuation criteria.

SUPPLEMENT ABSTRACTS

355

Complete response rate (CRR; primary endpoint) per 2014

Lugano Classiﬁcation, by central review, will be tested for the

intent‐to‐treat population between treatment arms using the

Cochran–Mantel–Haenszel method adjusted for stratiﬁcation fac-

tors from the randomization list. The trial is 99% powered for the

primary endpoint assuming a 55% CRR to Lonca and a 15% CRR

to idelalisib; the sample size for enrollment (∼150 pts) allows for a

robust safety data set. Secondary endpoints include overall

response rate (key secondary endpoint); progression‐free survival;

overall survival; duration of response; incidence and severity of

adverse events (AEs) and serious AEs; change from baseline in

laboratory values, vital signs, 12‐lead electrocardiogram, and

Eastern Cooperative Oncology Group performance status; con-

centration and pharmacokinetic parameters of Lonca total and

PBD‐conjugated Ab, and unconjugated warhead (SG3199); anti‐

drug Ab titers; and pt‐reported outcome (PRO) measures of

change from baseline in PROs (by EuroQol–5 Dimensions–5 Levels

and Functional Assessment of Cancer Therapy‐Lymphoma) and,

incidence, severity, and interference of speciﬁc symptomatic

AEs from the PROs version of the Common Terminology Criteria

for AEs.

EA – previously submitted to EHA 2021.

The research was funded by: ADC Therapeutics SA

Keywords: Indolent non‐Hodgkin lymphoma, Combination Therapies,

Ongoing Trials

Conﬂicts of interests pertinent to the abstract

C. Carlo‐Stella

Consultant or advisory role: Sanoﬁ, ADC Therapeutics, Roche, Kar-

yopharm Therapeutics, Celgene/Bristol‐Myers Squibb, Incyte

Honoraria: Bristol‐Myers Squibb, Merck Sharp & Dohme, Janssen

Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead Sciences

Research funding: ADC Therapeutics, Sanoﬁ, Roche

Educational grants: Roche, Janssen, ADC Therapeutics

J. Depaus

Consultant or advisory role: Takeda, Novartis, Janssen, AstraZeneca

B. T. Hess

Consultant or advisory role: ADC Therapeutics, Karyopharm

Therapeutics

Other remuneration: Bristol‐Myers Squibb, AstraZeneca (both

speaker's bureau)

P. L. Zinzani

Consultant or advisory role: ADC Therapeutics, Bristol‐Myers

Squibb, Celltrion, EUSA Pharma, Gilead Sciences, Janssen‐Cilag,

Kyowa Kirin, Merck Sharp & Dohme, Roche, Sandoz, Sanoﬁ, Servier,

Takeda, TG Therapeutics, Verastem Oncology

Other remuneration: Speaker's bureau: Bristo‐Myers Squibb, Cellt-

rion, EUSA Pharma, Gilead, Sciences, Janssen‐Cilag, Kyowa Kirin,

Merck Sharp & Dohme, Roche, Servier, Takeda, TG Therapeutics,

Verastem Oncology

D. Ungar

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

V. Dai

Employment or leadership position: ADC Therapeutics, SUNY

Research Foundation

Stock ownership: ADC Therapeutics

L. Wang

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

K. M. Ardeshna

Other remuneration: Autolus Therapeutics, Celgene

CAR‐T CELL THERAPY

265 |CARDIOVASCULAR EVENTS AMONG ADULT PATIENTS

WITH AGGRESSIVE B‐CELL LYMPHOMA TREATED WITH

STANDARD OF CARE AXICABTAGENE CILOLEUCEL AND

TISAGENLECLEUCEL

R. Steiner

, J. Banchs

, E. Koutroumpakis

, M. Becnel

, C. Gutierrez

P. Strati

, C. Pinnix

, L. Feng

, C. Claussen

, N. Palaskas

, K.

Karimzad

, S. Ahmed

, S. Neelapu

, E. Shpall

, M. Wang

, F. Vega

, J.

Westin

, L. Nastoupil

, A. Deswal

MD Anderson Cancer Center, Lymphoma & Myeloma, Houston, Texas,

USA,

MD Anderson Cancer Center, Cardiology, Houston, USA,

Anderson Cancer Center, Critical Care & Respiratory Care, Houston,

Texas, USA,

MD Anderson Cancer Center, Radiation Oncology, Houston,

Texas, USA,

MD Anderson Cancer Center, Biostatistics, Houston, Texas,

USA,

MD Anderson Cancer Center, Stem Cell Transplantation, Houston,

Texas, USA,

MD Anderson Cancer Center, Hematopathology, Houston,

Texas, USA

Introduction: Standard of care (SOC) Anti‐CD19 chimeric antigen

receptor (CAR) T‐cell therapies such as axicabtagene ciloleucel (axi‐

cel) and tisagenlecleucel (tisa‐cel) are associated with cytokine

release syndrome (CRS) and immune cell‐associated neurotoxicity

syndrome (ICANS).

There is limited information available about cardiovascular (CV)

events associated with SOC axi‐cel or tisa‐cel. In the clinical trials

leading to their FDA approval, patients with CV comorbidities, organ

dysfunction, or lower performance status were often not included.

An improved understanding of CV toxicities in the real‐world setting

will better guide therapy selection and management of patients

receiving these cellular therapies.

Methods: We retrospectively reviewed the characteristics and out-

comes of adult patients with relapsed/refractory large B‐cell lym-

phoma treated with SOC axi‐cel or tisa‐cel between 01/2018 and 4/

2020 at MD Anderson Cancer Center. Major adverse CV events

within 30 days after infusion (30‐d MACE) included arrhythmias

356

SUPPLEMENT ABSTRACTS

requiring intervention (ARI), new cardiomyopathy (NCMP), exacer-

bation of heart failure (HF), cerebrovascular accident (CVA),

myocardial infarction (MI), or CV death. MACE, CRS, and ICANS were

treated per institutional standards.

Results: One‐hundred and sixty‐ﬁve patients were included in the

analysis, and baseline characteristics are shown in the Table. Overall,

16% of patients developed at least one 30‐d MACE: 60.6% ARI (atrial

ﬁbrillation/ﬂutter 40.7%, non‐sustained ventricular tachycardia

40.7%), 12.1% EHF, 12.1% CVA, 6.1% MI, 6.1% NCMP, and one pa-

tient died due to MI. The ﬁrst 30‐d MACE occurred in a median of 7

days (range 0‐29) after CAR‐T cell infusion. Moreover, 6 patients had

one recurrence of 30‐d MACE (2 EHF, 2 ARI, and 2 CVA), and 3

SUPPLEMENT ABSTRACTS

357

patients experienced two recurrences of 30‐d MACE (1 ARI and 2

NCMP).

As displayed in the Table, age >60 years, baseline echocardio-

graphic diastolic dysfunction, earlier start of CRS, CRS ≥grade 3,

long duration of CRS, and use of tocilizumab were signiﬁcantly

associated with an increased risk of 30‐d MACE.

No association between timing and/or magnitude of C‐reactive

protein or ferritin peak and occurrence of MACE was observed.

After a median follow‐up time of 16.2 months (range 14.3‐19.1)

for censored observations, the occurrence of 30‐d MACE was not

signiﬁcantly associated with progression‐free survival (PFS) (p‐value

=0.55, log‐rank test), or with overall survival (OS) (p‐value =0.52,

log‐rank test).

Conclusions: Our results suggest that the occurrence of 30‐d MACE

is more frequent among patients who are elderly, with baseline dia-

stolic dysfunction, early, severe and prolonged CRS, but had no sta-

tistically signiﬁcant impact on PFS and OS. However, with limited

follow‐up, larger prospective studies are needed, and multidisci-

plinary management of these patients is recommended.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Cellular

therapies

Conﬂicts of interests pertinent to the abstract

R. Steiner

Research funding: Rafael Pharmaceuticals

C. Gutierrez

Consultant or advisory role: Advisory Board for Legend Biotech &

Janssen (2020 and 2021)

P. Strati

Consultant or advisory role: Consultant for Roche‐Genentech

S. Ahmed

Research funding: Research funding from Seattle genetics and Tessa

therapeutics

S. Neelapu

Consultant or advisory role: consultant to Kite, a Gilead Company,

Merck, Bristol‐Myers Squibb, Novartis, Celgene, Pﬁzer, Allogene

Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences,

Legend Biotech, Adicet Bio, Calibr, and Unum Therapeutics

Honoraria: received royalties from Takeda Pharmaceuticals,

Research funding: received research support from Kite, a Gilead

Company, Bristol‐Myers Squibb, Merck, Poseida, Cellectis, Celgene,

Karus Therapeutics, Unum Therapeutics, Allogene Therapeutics,

Precision Biosciences, and Acerta

Other remuneration: intellectual property related to cell therapy

E. Shpall

Consultant or advisory role: Consultant on Scientiﬁc Advisory

Boards: Bayer HealthCare Pharmaceuticals, Novartis, Magenta,

Adaptimmune, Mesoblast, Axio

Honoraria: Honorarium: Magenta, Novartis, Bayer HealthCare

Pharmaceuticals

Other remuneration: License Agreements or Patents: Takeda (EJ

Shpall is listed as a co‐inventor on a provisional patent application on

Takeda that is owned by MD Anderson and licensed to Takeda.

Afﬁmed

M. Wang

Consultant or advisory role: Consultancy – InnoCare, Loxo Oncology,

Juno, Oncternal, CStone, AstraZeneca, Janssen, VelosBio,

Honoraria: Janssen, Acerta Pharma, OMI, Physicians Education Re-

sources, Dava Oncology, CAHON, Hebei Cancer Prevention Feder-

ation, Clinical Care Options, Mumbai Hematology Group, Anticancer

Association, Newbridge Pharmaceuticals.

Research funding: Research Funding – Pharmacyclics, Janssen,

AstraZeneca, Celgene, Loxo Oncology, Kite Pharma, Juno, BioInvent,

VelosBio, Acerta Pharma, Oncternal, Verastem, Molecular Templates,

Lilly, Innocare.

F. Vega

Research funding: Research support from CRISP therapeutics

Other remuneration: Salary support from NCI/NIH R01 CA222918

J. Westin

Consultant or advisory role: Advisory: Kite, BMS, Novartis, ADC

Therapeutics, Iksuda, Genentech, AstraZeneca, Curis, Morphosys

Research funding: Clinical trial funding: Kite, BMS, Novartis, ADC

Therapeutics, Genentech, AstraZeneca, Curis, Morphosys, 47 Inc

L. Nastoupil

Honoraria: Honorarium: ADC Therapeutics, Bayer, BMS/Celgene,

Epizyme, Genentech, Gilead, Janssen, Novartis, Pﬁzer, TG

Therapeutics.

Research funding: Research funding: BMS/Celgene, Epizyme, Gen-

entech, Janssen, Novartis, Pﬁzer, Takeda, TG Therapeutics.

266 |PATIENT‐REPORTED QUALITY OF LIFE (QOL)

FOLLOWING TISAGENLECLEUCEL (TISA‐CEL) INFUSION IN

ADULT PATIENTS (PTS) WITH RELAPSED/REFRACTORY

FOLLICULAR LYMPHOMA (R/R FL)

N. H. Fowler

, M. Dickinson

, J. Martinez‐Lopez

, A. Kolstad

, S. J.

Schuster

, M. Dreyling

, M. Ghosh

, H. Harigae

, M. José Kersten

, E.

Bachy

, L. Popplewell

, J. C. Chavez

, P. J. Ho

, J. Butler

, K.

Kato

, B. von Tresckow

, A. J. M. Ferreri

, J. A. P. Simón

, P. E. M.

Patten

, C. Andreadis

, P. A. Riedell

, J. P. McGuirk

, L. J. Nas-

toupil

, T. Teshima

, F. Offner

, A. Petzer

, A. Viardot

, P. L.

Zinzani

, R. Malladi

, J. Zhang

, R. Tiwari

, V. Bollu

, A.

Masood

, C. Thieblemont

The University of Texas MD Anderson Cancer Center, Department of

Lymphoma‐Myeloma, Houston, Texas, USA,

Royal Melbourne Hospital,

Peter MacCallum Cancer Centre, Melbourne, Australia,

Hospital 12 De

Octubre, Complutense University, CNIO, Madrid, Spain,

Oslo University

358

SUPPLEMENT ABSTRACTS

Hospital, Department of Oncology, Oslo, Norway,

University of Penn-

sylvania, Lymphoma Program, Philadelphia, Pennsylvania, USA,

LMU

Klinikum, Medizinische Klinik III, Munich, Germany,

University of Mich-

igan, Michigan Medicine, Ann Arbor, Michigan, USA,

Tohoku University

Hospital, Department of Hematology and Rheumatology, Sendai, Japan,

Amsterdam UMC, University of Amsterdam, on behalf of HOVON/LLPC,

Department of Hematology, Amsterdam, Netherlands,

Université

Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon, France,

City of

Hope National Medical Center, Department of Hematology & Hemato-

poietic Cell Transplantation, Duarte, California, USA,

Mofﬁtt Cancer

Center, Department of Malignant Hematology, Tampa, Florida, USA,

Royal Prince Alfred Hospital and University of Sydney, Institute of

Haematology, Camperdown, Australia,

Royal Brisbane Hospital, Hae-

matology and Bone Marrow Transplant Unit, Herston, Australia,

Kyushu

University Hospital, Hematology, Oncology, & Cardiovascular Medicine,

Fukuoka, Japan,

University Hospital Essen, University of Duisburg‐

Essen, Clinic for Hematology and Stem Cell Transplantation, West German

Cancer Center, Essen, Germany,

IRCCS Ospedale San Raffaele,

Department of Onco‐hematology, Milan, Italy,

University Hospital Vir-

gen del Rocío, Instituto de Biomedicina de Sevilla (IBIS / CSIC / CIBER-

ONC), Universidad de Sevilla, Department of Hematology, Sevilla, Spain,

King's College Hospital and King's College London, Division of Cancer

Studies, London, UK,

University of California San Francisco, Helen Diller

Family Comprehensive Cancer Center, San Francisco, California, USA,

University of Chicago Medical Center, Department of Medicine, Chi-

cago, Illinois, USA,

University of Kansas Medical Center, Division of

Hematologic Malignancies and Cellular Therapeutics, Kansas City, Kansas,

USA,

The University of Texas MD Anderson Cancer Center, Department

of Lymphoma‐Myeloma, Houston, Texas, USA,

Hokkaido University

Hospital, Department of Hematology, Sapporo, Japan,

UZ Gent,

Department of Hematology, Gent, Belgium,

Ordensklinikum Linz GmbH

Elisabethinen, Internal Medicine I, Linz, Austria,

University Hospital of

Ulm, Department of Internal Medicine III, Ulm, Germany,

University of

Bologna, Institute of Hematology “Seràgnoli”, Bologna, Italy,

Cambridge

University Hospitals NHS Foundation Trust, Centre for Clinical Haema-

tology, Cambridge, UK,

Novartis Pharmaceuticals Corporation, Global

Value and Access, East Hanover, New Jersey, USA,

Novartis Healthcare

Pvt. Ltd, Biostatistics, Hyderabad, India,

Novartis Pharmaceuticals

Corporation, Health Economics and Outcomes Research, East Hanover,

New Jersey, USA,

Novartis Pharmaceuticals Corporation, Clinical

Development, East Hanover, New Jersey, USA,

Hôpital Saint‐Louis‐

Université de Paris, Service d'Hématologie‐Oncologie, Paris, France

Introduction: Patient‐reported QoL is an important endpoint in the

single‐arm phase II ELARA trial of tisa‐cel, which has demonstrated

efﬁcacy and favorable safety proﬁles in adult pts with r/r FL (Fowler

NH et al, ASH 2020). Here, we present patient‐reported QoL data

before and after tisa‐cel infusion in ELARA.

Methods: Eligible pts (≥18 y) had r/r FL (grades 1‐3A) after ≥2

lines of therapy or had failed autologous stem cell transplant

(autoSCT). Pts completed the Functional Assessment of Cancer

Therapy‐Lymphoma (FACT‐Lym) and Short Form‐36 Health Survey

v2 (SF‐36) at baseline, and at Months (Mo) 3 and 6 post tisa‐cel

infusion. For both instruments, a change score >0 indicated

improved QoL.

Results: As of September 28, 2020, 98 pts were enrolled and 97

received tisa‐cel (median follow‐up, 10.6 mo); 75% of pts had pre-

viously received ≥3 prior lines of therapy and 36% had relapsed after

autoSCT. QoL instruments were completed by 79 pts (81%) at

baseline, including 69 pts who had a complete or partial response.

FACT‐Lym and SF‐36 assessments were completed by 71 (74%) and

68 (71%) pts at Mo 3 and by 61 (65%) and 60 (64%) pts at Mo 6,

respectively. The FACT‐Lym subscales showed improvement in the

emotional, functional, and physical domains. Furthermore, no dete-

rioration in the social/family domain by Mo 6 was reported, although

minimal clinically important differences of 2 were not reached.

Similarly, numeric improvement was observed in mean change scores

from baseline through Mo 3 for the SF‐36 mental health component

scores and through Mo 6 for the physical health component scores,

including general health, vitality, physical functioning, role‐emotional,

and role‐physical. Overall, 40%‐49% of pts demonstrated clinically

meaningful improvements in QoL based on FACT‐Lym and SF‐36

at Mo 3. Furthermore, 68%‐83% of pts’ QoL did not deteriorate

(Table). Similar trends were observed at Mo 6. Additionally, mean

SUPPLEMENT ABSTRACTS

359

change scores for FACT‐Lym improved from baseline to Mo 3 and to

Mo 6.

Conclusions: These results demonstrate that clinically meaningful

improvements in QoL were observed in pts post tisa‐cel infusion.

The research was funded by: Novartis Pharmaceuticals Corporation

Keywords: Indolent non‐Hodgkin lymphoma, Cellular therapies

Conﬂicts of interests pertinent to the abstract

N. H. Fowler

Consultant or advisory role: Roche/Genentech, TG Therapeutics,

Verastem, Bayer, Celgene, Novartis

Research funding: Roche, Celgene, Gilead Sciences, TG Therapeutics,

Novartis, Abbvie, BeiGene

M. Dickinson

Consultant or advisory role: Novartis, Bristol‐Myers Squibb, Gilead

Sciences, Roche, Janssen

Honoraria: Roche, Amgen, MSD, Janssen, Bristol‐Myers Squibb,

Novartis

Research funding: Novartis, Roche, Takeda, Celgene, MSD

Educational grants: Roche

Other remuneration: Speakers' Bureau: Novartis

J. Martinez‐Lopez

Consultant or advisory role: Janssen, Novartis, BMS, Incite, Astellas,

Glaxo

Stock ownership: Altum Sequencing

Research funding: BMS, Roche

Other remuneration: Speakers' Bureau: Janssen, Novartis, BMS,

Incite, Astellas, Glaxo

A. Kolstad

Consultant or advisory role: Nordic Nanovector

Research funding: Merck, Nordic Nanovector

Educational grants: Nordic Nanovector

S. J. Schuster

Consultant or advisory role: Celgene, Nordic Nanovector, Novartis,

Abbvie, Acerta Pharma/AstraZeneca, Alimera Sciences, BeiGene,

Juno Therapeutics, Loxo Oncology, Tessa Therapeutics, Genentech/

Roche

Honoraria: Novartis, Celgene

Research funding: Novartis, Pharmacyclics, Adaptaive Bio-

technologies, Merck, Genentech/Roche, Celgene, Juno Therapeutics,

Abbvie, Incyte, TG Therapeutics, DTRM

Other remuneration: Patent Combination Therapies of CAR and PD‐

1 Inhibitors (via University of Pennsylvania with royalties to

Novartis)

M. Dreyling

Consultant or advisory role: Acerta Pharma/AstraZeneca; Bayer/Vi-

tal; Celgene/JAzz; Gilead Sciences; Janssen‐Cilag; Noavrtis; Roche;

Beigene

Research funding: Celgene; Janssen‐Cilag; Roche‐Pharma AG; Abbvie

Educational grants: Celgene; Janssen‐Cilag; Roche‐Pharma AG

Other remuneration: Bayer Health; Celgene; Gilead Sciences; Jans-

sen‐Cilag; Roche‐Pharma AG

M. Ghosh

Research funding: Novartis; BMS

H. Harigae

Honoraria: BMS, Novaritis, Chugai, Janssen

Research funding: Astellas

M. José Kersten

Consultant or advisory role: Novartis; Kite a Gilead Company; Mil-

tenyi Biotec; Takeda

Honoraria: Novartis; Kite a Gilead Company; Roche

Educational grants: Novartis; Kite a Gilead Company; Roche; Celgene

E. Bachy

Consultant or advisory role: Roche; Incyte

Honoraria: Roche; Janssen; Celgene; Novartis; Gilead

Research funding: Takeda; Amgen

Other remuneration: Roche; Beigene; Celgene; Abbvie

L. Popplewell

Honoraria: Pﬁzer; Roche

Educational grants: Novartis

J. C. Chavez

Consultant or advisory role: Kite/Gilead; Novartis; Bayer; Kar-

yopharm Therapeutics; Verastem; Pﬁzer; Morphosys; TeneoBio; Juno

Therapeutics; Celgene

Research funding: Merck

Other remuneration: Kite/Gilead; Genentech; AstraZeneca; BeiGene

P. J. Ho

Research funding: Abbvie; Celgene; La Jolla Pharma; Novartis; Pi

Square LLC; Takeda

J. Butler

Consultant or advisory role: Novartis

Other remuneration: Novartis

K. Kato

Consultant or advisory role: AbbVie; AstraZeneca; Celgene; Chugai;

Eisai; Janssen; Novartis; Daiichi Sankyo

Honoraria: Takeda; MSD; Kyowa‐Kirin; Janssen; Celgene; Ono;

Mundi; Dainippon‐Sumitomo; Bristol‐Myers‐Squibb

Research funding: Chugai; Takeda; Kyowa‐Kirin; AbbVie; Novartis;

Eisai; Janssen; Celgene; Ono; Daiichi Sankyo

B. von Tresckow

Honoraria: Amgen; Pﬁzer; Kite/Gilead; Roche; MSD; Takeda

Research funding: MSD; Takeda; Novartis

Educational grants: MSD; Takeda; Novartis

360

SUPPLEMENT ABSTRACTS

A. J. M. Ferreri

Consultant or advisory role: Gilead

Research funding: Gilead; Morphosys; Hutchinson; BMS

J. A. P. Simón

Consultant or advisory role: Novartis; Gilead; Jassen; JAZZ;Hono-

raria: Novartis ; Gilead; Jassen; JAZZ; AMGEN

Other remuneration: Gilead

P. E. M. Patten

Consultant or advisory role: Abbvie; Gilead; Janssen; Novartis; Roche

Honoraria: Abbvie; Astra Zeneca; Gilead; Janssen; Novartis; Roche

Research funding: Gilead

C. Andreadis

Consultant or advisory role: Gilead Sciences; Kite Pharma; Kar-

yopharm Therapeutics; Atara Biotherapeutics; Incyte; TG Therapeu-

tics; Epizyme

Research funding: Novartis; GlaxoSmithKline; Amgen; Jumo Thera-

peutics; Celgene; Merck

Educational grants: Gilead Sciences; Kite Pharma; ROche/Genentech

P. A. Riedell

Honoraria: Kite/Gilead; Celgene/BMS; Takeda; Verastem; Novartis;

Karyopharm Therapeutics; Bayer

Research funding: Kite/Gilead; Celgene/BMS; MorphoSys; Novartis;

Calibr

Other remuneration: Novartis

J. P. McGuirk

Consultant or advisory role: Juno Therapeutics; AlloVir

Honoraria: Kite Pharmaceuticals; Juno Therapeutics; AlloVir

Research funding: Novartis; Fresenius Biotech; Astellas; Bellicum

Pharmaceuticals; Kite Pharmaceuticals; Gamida Cell; Pluristem Ltd;

Juno Therapeutics; AlloVir

Other remuneration: Kite Pharmaceuticals

L. J. Nastoupil

Honoraria: Bayer; Celgene/BMS; Gamida Cell; Gilead/KITE; Janssen;

Novartis; Pﬁzer; TG Therapeutics; Genentech/Roche

Research funding: Celgene/BMS; Janssen; Karus Therapeutics; LAM

Therapeutics; Merck; Novartis; Pﬁzer; TG Therapeutics; Genentech/

Roche

T. Teshima

Consultant or advisory role: Merck Sharp & Dohme Corp; Takeda

Pharmaceutical Company Limited; Novartis Pharma K.K.

Honoraria: Merck Sharp & Dohme Corp; Kyowa Kirin Co., Ltd.;

Takeda Pharmaceutical Company Limited; Pﬁzer Japan Inc.; Bristol‐

Myers Squibb; TEIJIN PHARMA LIMITED.; Fuji Pharma Co., Ltd.;

NIPPON SHINYAKU CO.,LTD.

Research funding: Kyowa Kirin Co., Ltd.; Novartis Pharma K.

K.; Astellas Pharma Inc.; Chugai Pharmaceutical Co., Ltd.,; Sanoﬁ

K.K

Other remuneration: Kyowa Kirin Co., Ltd.; Novartis Pharma K.K.;

Janssen Pharmaceutical K.K.; Japan Society for the Promotion of

Science KAKENHI (17H04206); The Center of Innovation Program

from Japan Science and Technology Agency

A. Petzer

Consultant or advisory role: Novartis; Kite‐Gilead; Celgene; Roche;

Janssen; Amgen

Honoraria: Novartis; Kite‐Gilead; Celgene; Roche; Janssen; Amgen

A. Viardot

Consultant or advisory role: Amgen; Kite/Gilead; Roche

Honoraria: Pﬁzer; Roche

Educational grants: Abbvie; Bristol‐Myers Squibb; Janssen; Kite, a

Gilead company; Roche

P. L. Zinzani

Employment or leadership position: Servier; EUSA Pharma

Honoraria: Servier; Takeda; TG Therapeutics; Gilead; Merck; BMS;

Roche; EUSA Pharma; Verastem; Janssen; Kirin Kyowa; DC Thera-

peutics; Abbvie

Other remuneration: Servier; Takeda; TG Therapeutics; Gilead;

Merck; BMS; Roche; EUSA Pharma; Verastem; Janssen; Kirin Kyowa;

DC Therapeutics; Abbvie

R. Malladi

Consultant or advisory role: Novartis

Honoraria: Novartis

J. Zhang

Employment or leadership position: Novartis Pharmaceutical

Corporation

Stock ownership: Novartis Pharmaceutical Corporation

R. Tiwari

Employment or leadership position: Novartis Pharmaceutical

Corporation

Stock ownership: Novartis Pharmaceutical Corporation

V. Bollu

Employment or leadership position: Novartis Pharmaceutical

Corporation

Stock ownership: Novartis Pharmaceutical Corporation

A. Masood

Employment or leadership position: Novartis Pharmaceutical

Corporation

Stock ownership: Novartis Pharmaceutical Corporation

C. Thieblemont

Honoraria: Celgene; Abbvie; Bayer; Janssen; Roche; Incyte; Novartis;

Gilead Sciences

Research funding: Roche

Educational grants: Roche; Janssen‐Cilag; Kite/Gilead; Novartis

SUPPLEMENT ABSTRACTS

361

267 |SAFETY AND EFFICACY OF TISAGENLECLEUCEL PLUS

PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY

DIFFUSE LARGE B‐CELL LYMPHOMA: UPDATED ANALYSIS OF

THE PHASE 1B PORTIA STUDY

U. Jaeger

, N. Worel

, J. P. McGuirk

, P. A. Riedell

, I. Fleury

, P.

Borchmann

, Y. Du

, X. Han

, M. Martinez‐Prieto

, E. K. Waller

Medical University of Vienna, Vienna, Austria,

Medical University of

Vienna, Vienna, Austria,

Division of Hematologic Malignancies and

Cellular Therapeutics, University of Kansas Medical Center, Kansas

City, USA,

University of Chicago, Chicago, USA,

Maisonneuve‐

Rosemont Hospital, University of Montreal, Montreal, Canada,

Uni-

versity Hospital Cologne, Cologne, Germany,

Novartis Pharma AG,

Shanghai, China,

Novartis Pharmaceuticals Corporation, East Hanover,

USA,

Novartis Oncology, Novartis Pharmaceuticals Corporation, East

Hanover, USA,

Emory University Winship Cancer Institute, Atlanta,

Georgia, USA

Background: Tisagenlecleucel (Tisa‐cel) showed durable responses

and manageable safety in patients (pts) with relapsed/refractory

diffuse large B‐cell lymphoma (r/r DLBCL) in the JULIET trial. High

baseline programmed cell death 1 (PD‐1) expression associated with

higher probability of no response (Schuster et al. NEJM 2019). Here

we report an updated analysis of PORTIA, a phase 1b, multicenter,

open‐label study of tisa‐cel plus pembrolizumab (pembro) in pts with

r/r DLBCL (NCT03630159).

Methods: Eligible pts (≥18 y) had r/r DLBCL after ≥2 lines of therapy

and relapsed after or were not candidates for autologous stem cell

transplant (autoSCT). Pts received a single tisa‐cel infusion on Day 1

and were enrolled in 1 of 3 cohorts that initiated pembro (200 mg q 21

days, up to 6 doses) on either Days +15, +8, or –1. Primary endpoints

were incidence of dose‐limiting toxicities (DLTs) and overall response

rate (ORR; complete response [CR] and partial response [PR]). Sec-

ondary endpoints included duration of response, progression‐free

survival, overall survival, safety, and cellular kinetics.

Results: As of November 9, 2020, 15 pts were enrolled and 12

received tisa‐cel (n =4 pts for each Days +15, +8, and –1 cohorts;

median follow‐up, 4 mo). At study entry, the median age among

treated pts was 62 y (range, 35‐79), 100% had an International

Prognostic Index score ≥2, 67% had ≥3 prior lines of therapy, 58%

had stage IV disease, 58% had lactate dehydrogenase >ULN, and

42% had prior autoSCT. All 12 pts had ≥1 AE. Grade ≥3 AEs

suspected to be related to tisa‐cel and/or pembro were neutropenia

(n =4); neutrophil count decreased (n =3); febrile neutropenia,

lymphocyte count decreased, malnutrition (each n =2); anemia,

leukopenia, diarrhea, white blood count decreased, liver function

tests increased, thrombocytopenia, hepatitis, and cytokine release

syndrome (CRS; each n =1). No neurotoxicity or DLTs were

observed. Among the Day +15, +8, and –1 cohorts (each n =4), the

ORR was 50% (2/4; CR n =0, PR n =2), 25% (1/4; CR n =1, PR n =

0), and 25% (1/4; CR n =1, PR n =0; longer follow‐up is needed for n

=2 pts), respectively. Tisa‐cel exposure and peak expansion were

consistent with JULIET, with a trend toward delayed expansion in the

Day –1 cohort (n =4). There was no sign of secondary expansion

following pembro administration regardless of the number of doses.

Compared with JULIET, lower CRS severity and frequency and lower

cytokine proﬁles were observed for all 3 cohorts.

Conclusions: The combination of tisa‐cel plus pembro was feasible

and showed manageable safety. The lack of improved efﬁcacy in

PORTIA with the addition of pembro compared with tisa‐cel alone

may be related to more pts with ≥3 prior lines of therapy (67% vs

51%, respectively), and/or pts with more advanced disease in

PORTIA. Additional studies with larger patient cohorts are needed to

determine the value of adding PD‐1 inhibitors to CAR‐T cell therapy

in pts with r/r DLBCL.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: Novartis Pharmaceuticals Corporation

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Non‐Hodgkin

(Pediatric, Adolescent, and Young Adult)

Conﬂicts of interests pertinent to the abstract

U. Jaeger

Consultant or advisory role: Novartis, Celgene/BMS, Miltenyi Biotec,

CDR‐Life

Honoraria: Abbvie, Novartis, Gilead, Celgene/BMS, Karyopharm

Therapeutcis, Miltenyi Biotec, Roche

Research funding: To Institution‐Novartis, Gilead, Celgene/BMS,

CDR‐Life, Roche

N. Worel

Consultant or advisory role: Novartis, Celgene/BMS

Research funding: To Institution‐Sanoﬁ

Educational grants: Therakos/Mallinkrodt, Celgene/BMS

Other remuneration: Speaker Bureau‐Sanoﬁ, Novartis, Kite/Gilead,

Therakos/Mallinkrodt

J. P. McGuirk

Consultant or advisory role: Kite, Juno, Allovir, Magenta Therapeu-

tics, EcoR1 Cap

Honoraria: Kite, Allovir, Juno, Magenta Therapeutics

Research funding: To Institution‐Novartis, Fresenius Biotech, Astel-

las, Bellicum, Gamida Cell, Pluristem Therapeutics, Kite, Allovir

Educational grants: Kite

Other remuneration: Speakers' Bureau‐Kite

P. A. Riedell

Honoraria: Kite, Celgene/BMS, Takeda Verastem, Novartis, Kar-

yopharm Therapeutics, Bayer

Research funding: To Institution‐Kite. Celgene/BMS, MorphoSys,

Novartis, Calibr

Other remuneration: Novartis

I. Fleury

Consultant or advisory role: Abbvie, AstraZeneca, Gilead, Janssen,

Novartis, Roche, Seattle Genetics

Honoraria: Abbvie, Gilead, Janssen, Novartis, Roche, Seattle Genetics

362

SUPPLEMENT ABSTRACTS

Y. Du

Employment or leadership position: Novartis Pharmaceuticals

Corporation

X. Han

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

M. Martinez‐Prieto

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

Honoraria: Novartis Pharmaceuticals Corporation

E. K. Waller

Employment or leadership position: Cambium Medical Technologies

Consultant or advisory role: Novartis, Verastem, Pharmacyclics,

Karyopharm, Partners Healthcare, Kite,

Stock ownership: Cambium Medical Technologies, Cerus, Chimerix

Honoraria: Novartis, Verastem, Pharmacyclics, Karyopharm, Partners

Healthcare, Kite,

Research funding: Novartis, Amgen, Juno, Verastem, Partners

Healthcare

Educational grants: Pharmacyclics

Other remuneration: Royalties from patent on platelet lysate that

has been licensed to Cambuim Medical Technologies

268 |RELAPSE CHARACTERIZATION IN DIFFUSE LARGE B

CELL LYMPHOMA PATIENTS UNDERGOING COMMERCIAL CAR‐

T CELL THERAPY: EXPERIENCE FROM A SINGLE CENTRE

M. Bastos‐Oreiro

, R. Bailén

, P. Silva

, S. Monsalvo

, A. Pérez

Corral

, D. Carbonell

, F. Díaz Crespo

, I. Gómez‐Fernández

, G.

Oarbeascoa

, N. Dorado

, C. Muñoz

, S. Sabell

, J. Menarguez

, C.

Martínez‐Laperche

, I. Buño

, J. Anguita Velasco

, J. L. Díez‐Martín

M. Kwon

Hospital Universitario Gregorio Marañón, *equal contribution,

Hematology, Madrid, Spain,

Hospital Universitario Gregorio Marañón,

Hematology, Madrid, Spain,

Hospital Universitario Gregorio Marañón,

Pathology, Madrid, Spain,

Hospital Universitario Gregorio Marañón,

Medicina Nuclear, Madrid, Spain

Background: CAR‐T cell therapy is approved for the treatment of

adults with relapsed or refractory (R/R) diffuse large B‐cell lym-

phoma (DLBCL). However, 40‐60% of patients relapse after therapy

and characterization of relapse has been poorly reported.

Aims: To describe relapse characteristics in biopsy samples in pa-

tients with DLBCL receiving CAR‐T cell therapy in our center.

Methods: All consecutive patients diagnosed with R/R DLBCL who

were infused with commercial CAR‐T cells from June 2019 to

December 2020 were included.

CAR‐T cell expansion in PB was monitored by multiparameter

ﬂow cytometry (FC) through detection of labeled CD19 in T cells

(Human CD19 Protein®). PET‐CT scanner evaluation was performed

on days +30, +90 and +180. In cases where PET‐CT detected pro-

gression or indeterminate response, core‐needle biopsy of the

accessible lesions was performed. Study of biopsy included: histo-

logical analysis; FC immune phenotyping including CAR‐T cell pres-

ence and detection of exhausted CD3+populations (LAG3, TIM3,

PD1). DNA was puriﬁed from biopsy using GeneRead DNA FFPE Kit

(Qiagen). Mutations of CD19 (exon2‐5) were analyzed by Sanger

sequencing.

Results: 30 patients with R/R lymphoma were treated: 21 with axi‐

cel 9 with tisa‐cel. Median age at infusion was 57 years (r: 22‐79);

16 (53%) were female. Median follow up‐was 9.5 months (r: 3‐18).

PFS at 6 months was 42% and OS 72%. CAR‐T cell expansion in PB

was detected in 29 patients (97%). Complete and overall response

TABLE 1Characteristics of the population at replapse

SUPPLEMENT ABSTRACTS

363

rate at day 30 (CR and ORR) were 39% and 75%, respectively (28

evaluable patients), and 41% and 55% at day 100, respectively (27

evaluable patients). At day 180, 10 out of 14 evaluable patients

(38.5%) showed CR. A total of 15 patients experienced relapse or

progression. Biopsy of the accessible lesions was performed in 10

(66%) (Table 1). Relapsed was conﬁrmed in all cases except in one in

whom sample was insufﬁcient. Three patients who were CD19+by

IHQ on the pre‐infusion biopsy showed CD19‐at relapse. CAR‐T cell

in PB at relapse was detected in all except one patient that did not

expand CAR‐T after 2 infusions and 60% of patients presented CAR‐

T in the biopsy. TME (tumor microenvironment) TCD3+lymphocytes

were >20% in 80% of the cases and no patient had <5%. In tumor

sample, FC failed to identify cellularity in 37% of patients; in the rest

of samples, percentage of exhausted TCD3 presented an average of

80% (range 64‐84). CD19 study revealed mutation in one patient (p.

V279L) who presented a CD19+relapse.

Conclusions: In our series of relapsed lymphomas after CAR‐T anti‐

CD19 treatment, CAR‐T cell was present in all patients in PB but

only 60% in tissue. CD19 loss and mutations in DNA are possible

relapse mechanisms. Exhausted TCD3 lymphocytes were abundant in

TME, which would support its relevant role preventing a good

function of the carts in situ. More complex biopsies analyses are

necessary to better understand relapse mechanisms.

Keywords: Tumor Biology and Heterogeneity, Aggressive B‐cell non‐

Hodgkin lymphoma, Cellular therapies

No conﬂicts of interests pertinent to the abstract.

269 |A SINGLE‐ARM, OPEN‐LABEL, PILOT TRIAL OF

AUTOLOGOUS CD7‐CAR‐T CELLS FOR CD7 POSITIVE RELAPSED

AND REFRACTORY T‐LYMPHOBLASTIC LEUKEMIA/LYMPHOMA

M. Zhang

, M. Zhang

, X. Fu

, H. Meng

, D. Chen

, M. Wang

, L.

Zhang

, L. Li

, X. Li

, X. Wang

, Z. Sun

, H. Yu

, Z. Li

, F. Nan

, Y.

Chang

, Z. Zhou

, J. Yan

, J. Li

, Y. Wang

, F. You

, Y. Wang

, S.

Xiang

, Y. Chen

, G. Pan

, H. Xu

, B. Zhang

, L. Yang

The First Afﬁliated Hospital of Zhengzhou University, Department of

Oncology, Zhengzhou, China,

PersonGen BioTherapeutics (Suzhou) Co.,

Ltd., PersonGen BioTherapeutics (Suzhou) Co., Ltd., Suzhou, China,

PersonGen‐Anke Cellular Therapeutics Co., Ltd, PersonGen‐Anke Cellular

Therapeutics Co., Ltd, Suzhou, China

Introduction: T lymphoblastic leukemia/lymphoma (T‐ALL/LBL) is

highly aggressive. Although intensive chemotherapies such as ALL‐

type regimens are commonly used, about half patients eventually

relapse and die of T‐ALL/LBL. Chimeric antigen receptor (CAR) T

cells have given rise to breakthroughs in treating B cell hematological

malignancies. However, there are few clinical studies of CAR‐T on T

cell malignant tumors. CD7, overexpressed in up to 100% of

relapsed/refractory T‐ALL/LBL, is an attractive therapeutic target for

T‐lymphoblastic leukemia/lymphoma (T‐ALL/LBL). Now, a nanobody

derived CD7‐CAR‐T with a highly optimized structure and a clinically

feasible strategy to overcome CAR‐T cell fratricide and exclude

abnormal T cell contamination have been developed. Pre‐clinical

studies have demonstrated CD7 CAR T cells produced robust cyto-

toxicity against malignant T‐cell lines and primary tumors and were

protective in a mouse xenograft model of T‐ALL.

Method: This is a single‐arm, open label, safety and efﬁcacy pilot

study (NCT04004637). Study participants will receive Flu/Cy pre‐

treatment before CAR‐T infusion. CD7 CAR‐T was then adminis-

tered at a single dose of 1.0 �10

(N =5) or 1.5 �10

(N =1; Pt#1)

or 2 �10

(N =3; Pt#7, 8, 9) CAR‐T cells/kg. Adverse events were

categorized by NCI‐CTCAE V5.0. Tumor response were assessed

based on the 2014 Lugano Evaluation Criteria for Lymphoma and

2016 Chinese Guideline for Diagnosis and Treatment of Acute

Lymphoblastic Leukemia.

Results: Up to now, a total of 9 patients including 6 r/r T‐ALL/LBL

and 3 r/r ETP‐ALL/LBL (case 4, 5, 6) were assigned to receive CD7

CAR‐T cell and completed the efﬁcacy assessment. Overall response

rate at 1 month was 100%. In patients followed up for ≥3 months,

complete remission (CR) rate at 3 month was 71.4%. Case 1‐6 was

administered at 1.0�10

CAR‐T/Kg except for case 1 (1.0 �10

CAR‐T/Kg). Bone marrow (BM) tumor burden of case 1 decreased

from 70.03% to 19.51% and case 1 has an OS more than 15 months.

Case 2 died due to abdominal infection at 3 month although he was

still in MRD‐status then. Case 3 had sustained MRD‐for 7 months

but appeared MRD+in BM at 8 month, so second CD7 CAR‐T

infusion had been performed and patient achieved CR at 14th day.

Case 4 has been achieving CR more than 9 months and is still in

remission. Case 5 and 6 had a DOR (Duration of response) of about 4

and 3 months respectively. In case 1‐6, despite case1‐2 appeared

grade 2 CRS, all other cases only had grade 1. Therefore, in order to

further explore the best effective dose, case 7‐9 had received dose of

2.0 �10

CAR‐T/Kg. Case 8‐9 are still in complete remission.

Unfortunately, case 6 relapsed at 6 month due to CD7 negative

blasts. The absence of CD7 on the cell surface enables the tumor to

evade CAR T cell‐mediated recognition and clearance, despite

continued persistence of CAR‐T cells.

Conclusions: Autologous CD7 CAR‐T is a novel immunotherapy for

r/r T‐ALL/LBL and exhibited encouraging clinical efﬁcacy and safety

in treating r/r T‐ALL/LBL and ETP‐ALL/LBL.

The research was funded by: Comprehensive and Digital Technology

Demonstration Platform for Clinical Evaluation of New Drugs for

Major Diseases, National Key Research and Development Project,

(2020ZX09201‐009)

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma, Cellular ther-

apies, Immunotherapy

Conﬂicts of interests pertinent to the abstract

H. Meng

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

364

SUPPLEMENT ABSTRACTS

D. Chen

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

M. Wang

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

Y. Wang

Employment or leadership position: PersonGen‐Anke Cellular Ther-

apeutics Co., Ltd.

F. You

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

Y. Wang

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

S. Xiang

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

Y. Chen

Employment or leadership position: PersonGen‐Anke Cellular Ther-

apeutics Co., Ltd.

G. Pan

Employment or leadership position: PersonGen‐Anke Cellular Ther-

apeutics Co., Ltd.

H. Xu

Employment or leadership position: PersonGen‐Anke Cellular Ther-

apeutics Co., Ltd.

B. Zhang

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

L. Yang

Employment or leadership position: PersonGen BioTherapeutics

(Suzhou) Co., Ltd.

270 |PATIENTS WITH OUT OF SPECIFICATION

TISAGENLECLEUCEL CAN BE SALVAGED WITH A POINT‐OF‐

CARE CAR T‐CELLS: AN OBSERVATIONAL INTENTION‐TO‐TREAT

SINGLE‐CENTER ANALYSIS

S. Fried

, R. Shouval

, N. Varda‐Bloom

, M. Besser

, R. Yerushalmi

N. Shem‐Tov

, I. Danylesko

, E. Jacoby

, S. Teihman

, A. Shimoni

, A.

Nagler

, A. Avigdor

Chaim Sheba Medical Center, Division of Hematology and Bone Marrow

Transplantation, Tel Hashomer, Israel,

Memorial Sloan Kettering Cancer

Center, Adult BMT Service, New York, USA,

Chaim Sheba Medical

Center, Hematology Laboratory, Tel Hashomer, Israel,

Chaim Sheba

Medical Center, Ella Lemelbaum Institute for Immuno Oncology, Tel

Hashomer, Israel,

Chaim Sheba Medical Center, Department of Pediatric

Hematology‐Oncology, Safra Children's Hospital, Tel Hashomer, Israel

Introduction: Tisagenlecleucel (Tisa‐cel) is an anti‐CD19 chimeric

antigen receptor (CAR) T‐cell therapy approved for patients (pts)

with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL).

Results from the JULIET trial showed best overall response of 52%

per protocol and 34% in an intention‐to‐treat (ITT) analysis. Out-

comes of pts with out of commercial speciﬁcation (OOS) products are

not well established. Availability of point‐of‐care anti‐CD19/CD28

costimulatory domain academic CAR T‐cells in our center allows us

SUPPLEMENT ABSTRACTS

365

to provide rapid salvage in cases of commercial CAR T‐cell produc-

tion failure.

Methods: Data of pts who underwent leukapheresis for Tisa‐cel in a

single center were collected. Survival was calculated from

leukapheresis.

Results: Peripheral blood cells were collected from 37 pts with

DLBCL between 05/2019 and 02/2020. Median age at leukapheresis

was 63 (range 28‐79) years. Median number of prior therapies was 2

(range 2‐6). Cells from 78% of the pts were collected in progressive

disease. Bridging therapy was given to 87% of pts. Median time from

leukapheresis to cell infusion was 1.6 (range 1.3‐2.2) months. During

this time, disease progression was marked in 45% of the pts. Tisa‐cel

CAR T‐cells were infused in 29 (78%) of the pts. Median follow‐up is

14.7 months.

In 9 (24%) pts, manufactured Tisa‐cel did not meet speciﬁcations

for commercial release. Causes for OOS were production termination

(3 [33%]), low CAR viability (<70%; [33%]) and low CAR dose (<0.6 �

; [33%]). Among pts with OOS products, 3/9 (33%) received Tisa‐

cel despite not meeting production standards; 2/9 (22%) did not

receive Tisa‐cel due to disease progression; and 4/9 (44%) were

salvaged with point‐of‐care CAR T‐cells, at a median of 35 (range 16‐

92) days following OOS notiﬁcation. Three of these four pts achieved

a complete response (CR) (Figure 1A). In a univariate analysis, risk

factors for OOS were ≥4 prior therapies (p =0.04) and exposure to

bendamustine (p =0.04). Bone marrow transplantation and age ≥65

were not signiﬁcant risk factors.

Overall response at day‐28 post‐CAR T was 46% (CR 24%) and

35% (CR 24%) per protocol (i.e., including only pts received Tisa‐cel)

and in ITT (i.e., including all pts underwent leukapheresis), respec-

tively. One year overall survival (OS) was 65% (95% CI 50‐85%) per

protocol and 56% (95% CI 42‐75%) in ITT (Figure 1B). In a multi-

variable ITT Cox regression, factors associated with a shorter OS

were ECOG ≥2 (HR 6.5; 95% CI 1.9‐22.5) and primary refractory

disease (HR 3.3; 95% CI 1.2‐9.1). OOS was not a signiﬁcant risk factor

for a shorter OS (p =0.07), nor age, disease stage, and LDH at

leukapheresis.

Conclusion: Our data show relatively high rates of OOS products

following leukapheresis for Tisa‐cel. We highlight the ability to

rapidly produce point‐of‐care CAR T‐cells, facilitating immune‐

effector cell salvage of pts who experienced production failure of

the commercial product.

EA – previously submitted to EHA 2021.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Cellular

therapies

No conﬂicts of interests pertinent to the abstract.

271 |EXTRANODAL DISEASE IS ASSOCIATED WITH SHORTER

PROGRESSION‐FREE SURVIVAL AFTER CD19‐CAR T‐CELL

THERAPY FOR RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL

LYMPHOMA

V. Bücklein

, V. Blumenberg

, J. Ackermann

, L. Frölich

, M.

Winkelmann

, C. Schmidt

, K. Rejeski

, M. Ruzicka

, N. Müller

, L. von

Baumgarten

, F. Schöberl

, M. Hildebrandt

, A. Humpe

, W. Kunz

, E.

Hoster

, M. von Bergwelt

, M. Subklewe

University Hospital, LMU Munich, Department of Medicine III, Munich,

Germany,

University Hospital, LMU Munich, Department of Radiology,

Munich, Germany,

University Hospital, LMU Munich, Department of

Neurosurgery, Munich, Germany,

University Hospital, LMU Munich,

Department of Neurology, Munich, Germany,

University Hospital, LMU

Munich, Department of Transfusion Medicine, Munich, Germany,

LMU

FIGURE 1A Patients‘ outcome after Tisa‐cel OOS

FIGURE 1B Overall survival in an intention‐to‐treat analysis

366

SUPPLEMENT ABSTRACTS

Munich, Institute for Medical Information Processing, Biometry, and

Epidemiology, Munich, Germany

Introduction: CD19 CAR T cells induce complete remissions in ≥40%

of heavily pretreated patients with relapsed/refractory (r/r) diffuse

large B‐cell lymphoma (DLBCL). However, a signiﬁcant proportion of

patients progress early after therapy. Thus, to prospectively identify

patients most suitable for currently available commercial CAR T‐cell

products, we assessed the predictive value of clinical and laboratory

parameters for PFS in r/r DLBCL patients treated with Axicabtagene

Ciloleucel or Tisagenlecleucel at our institution.

Methods: Patient, disease, and treatment characteristics of r/r

DLBCL patients treated with CD19‐CAR T cells were retrospectively

assessed. Pre‐deﬁned patient and lymphoma characteristics known

to confer adverse outcomes in DLBCL were evaluated for their as-

sociation with PFS by univariable log‐rank tests, as well as multi-

variable stepwise Cox regression analyses. Characteristics

encompassed age, refractoriness to ﬁrst‐line therapy, no. of prior

therapy lines, tumor volume, presence of bulky disease, presence of

extranodal disease (END), Ann Arbor stage, IPI, LDH, and ECOG, all

assessed at time of lymphodepletion.

Results: As of November 2020, 35 patients have been transfused.

Median age was 60 years (range 19‐82). ECOG was 0‐1 in 23, and 2‐

3 in twelve patients at CAR T‐cell transfusion. Only 3 of the 35

transfused patients (9%) would have met the inclusion criteria of the

pivotal clinical trials at all eligibility assessment timepoints (enrol-

ment, apheresis, and time of lymphodepletion).

CRS occurred in 32/35 patients (80% CRS °1‐2, 11% °3). 16

patients (46%) experienced ICANS (29% °1‐2, 14% °3‐4, and 3% °5).

Response assessment after three months was available for 34/35

patients. Objective response rate was 53%, with complete remission

in 15 (44%) and partial remission in three patients (9%).

In univariable analyses, apart from primary refractory disease

(p =0.79), all pre‐selected characteristics were suggestive to be

associated with shorter PFS (p =0.002‐0.061). We therefore

included these variables (p <0.1) in multivariable Cox regression

analyses. In the resulting model, presence of END was associated

with inferior PFS (Hazard ratio [HR] 11.3, p =0.02), adjusted for

prior therapy lines (HR 1.3, p =0.06) and ECOG >1 (HR 2.3, p =

0.12). Other variables did not improve the prognostic validity of the

model.

Conclusions: We provide real‐world evidence that CD19‐CAR T cells

induce remissions in a substantial proportion of r/r DLBCL patients,

despite very frequent non‐eligibility for pivotal clinical trials in our

patient cohort. Extranodal disease at transfusion was associated with

signiﬁcantly shorter PFS both in uni‐and multivariable analyses. To

address END‐associated resistance mechanisms, we have set up a

comprehensive translational research program with speciﬁc focus on

the nodal vs. extranodal lymphoma microenvironment.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Cellular

therapies

Conﬂicts of interests pertinent to the abstract

V. Bücklein

Consultant or advisory role: Pﬁzer, Amgen, Kite Gilead

Research funding: Novartis, Celgene, Kite Gilead

272 |COMPARATIVE EFFICACY OF TISAGENLECLEUCEL (TISA‐

CEL) AND LISOCABTAGENE MARALEUCEL (LISO‐CEL) IN

RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA

(R/R DLBCL)

R. T. Maziarz

, J. Zhang

, H. Yang

, A. Agarwal

, W. Tang

, M.

Martinez‐Prieto

, V. Bollu

, D. Kuzan

, S. J. Schuster

, M. J. Kersten

Knight Cancer Institute, Oregon Health and Science University, Portland,

Oregon, USA,

Novartis Oncology, Novartis Pharmaceuticals Corporation,

East Hanover, USA,

Analysis Group, Inc., Boston, USA,

Novartis

Oncology, Novartis Pharmaceuticals Corporation, East Hanover, USA,

Analysis Group, Inc., Boston, USA,

Novartis Oncology, Novartis

Pharmaceuticals Corporation, East Hanover, USA,

Novartis US Oncology,

Novartis Pharmaceuticals Corporation, East Hanover, USA,

Novartis

Oncology, Novartis Pharmaceuticals Corporation, East Hanover, USA,

Lymphoma Program, Abramson Cancer Center of the University of

Pennsylvania, Philadelphia, USA,

Academic Medical Center, University

of Amsterdam, Amsterdam, Netherlands

Introduction: Chimeric antigen receptor T‐cell therapies tisa‐cel and

liso‐cel are effective treatments for r/r DLBCL (Schuster 2019,

Abramson 2020). This study compared efﬁcacy outcomes of tisa‐cel

and liso‐cel in r/r DLBCL using matching‐adjusted indirect compari-

son (MAIC).

Methods: Individual patient‐level data (IPD) from JULIET (tisa‐cel;

NCT02445248; 02/2020 datacut) were weighted to match the pa-

tient population in TRANSCEND (liso‐cel; NCT02631044; 08/2019

datacut). Baseline prognostic factors available in both trials were

adjusted for age, sex, histology, ECOG performance status [ECOG

PS], left ventricular ejection fraction, radiologic sum of product di-

ameters, lactate dehydrogenase, prior stem cell transplantation

[SCT], use of bridging therapy, and number of and refractoriness to

prior therapies, in the MAIC. Overall survival (OS), progression‐free

survival (PFS), complete response (CR) rate, and overall response

(OR) rate were compared. Primary analyses compared infused pa-

tients in JULIET (N =106, excluding 8 without lymphodepleting

chemotherapy [LDC] and 1 large cell neuroendocrine carcinoma)

with efﬁcacy‐evaluable set in TRANSCEND (N =256, infused pa-

tients). A scenario analysis compared JULIET infused to TRAN-

SCEND primary analysis set (PAS) (N =133, dose level 2, excluding

those with ECOG PS 2, prior allogeneic SCT, primary mediastinal B‐

cell lymphoma, follicular lymphoma [FL] 3B, or transformation from

indolent lymphoma besides FL). Sensitivity analyses included JULIET

patients with only ﬂudarabine‐based LDC or only adjusted signiﬁ-

cantly different baseline prognostic factors. Safety outcomes were

not compared because adverse event management has evolved and

differed between the two trials; MAIC is unable to adjust for such

differences.

SUPPLEMENT ABSTRACTS

367

Results: After adjusting for differences in baseline characteristics,

OS, PFS, and CR were comparable between tisa‐cel infused patients

and the liso‐cel efﬁcacy‐evaluable set (Table). The results were

consistent across all scenario and sensitivity analyses. OR rate

trended higher in the TRANSCEND efﬁcacy‐evaluable set (72.7% vs.

62.9%, p =0.07) and was higher in TRANSCEND PAS than in the

respectively matched JULIET infused set (74.4% vs. 60.9%, p <0.05).

Conclusions: The MAIC results indicate there is no evidence sug-

gesting differences in OS, PFS and CR between tisa‐cel and liso‐cel in

r/r DLBCL. Analyses using IPD from both trials and/or real‐world

evidence are warranted to conﬁrm these ﬁndings.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: Novartis Pharmaceuticals Corporation

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

R. T. Maziarz

Employment or leadership position: Knight Cancer Institute, Oregon

Health and Science University

Consultant or advisory role: Novartis, Incyte, Kite Pharmaceuticals,

Bristol‐Myers Squibb, Intellia, Artiva Therapeutics

Honoraria: Novartis, Omeros, PACT Pharmaceuticals

Educational grants: Novartis, Incyte, Kite Pharma

J. Zhang

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

H. Yang

Employment or leadership position: Analysis Group

A. Agarwal

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

W. Tang

Employment or leadership position: Analysis Group

M. Martinez‐Prieto

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

Honoraria: Novartis Pharmaceuticals Corporation

V. Bollu

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

D. Kuzan

Employment or leadership position: Novartis Pharmaceuticals

Corporation

Stock ownership: Novartis Pharmaceuticals Corporation

S. J. Schuster

Employment or leadership position: University of Pennsylvania

Consultant or advisory role: Celgene, Nordic Nanovector, Novartis,

Abbvie, Acerta Pharma/AstraZeneca, Alimera Sciences, BeiGene,

Juno Therapeutics, Loxo Oncology, Tessa Therapeutics, Genentech/

Roche

Research funding: To Institution‐Novartis, Pharmacyclics, Adaptive

Biotechnologies, Merck, Genentech/Roche, Celgene, Juno Thera-

peutics, Abbvie, Incyte, TG Therapeutics, DTRM

Other remuneration: Patent Combination Therapies of CAR and PD‐

1 Inhibitors (via University of Pennsylvania with royalties to

Novartis)

M. J. Kersten

Employment or leadership position: University of Amsterdam

Consultant or advisory role: Novartis, Kite, Miltenyi Biotech, Takeda

Honoraria: Novartis, Kite, Roche

Research funding: To Institution‐Kite

Educational grants: Novartis, Kite, Roche, Celgene

273 |OUTREACH: PRELIMINARY SAFETY & EFFICACY

RESULTS FROM A PHASE 2 STUDY OF LISOCABTAGENE

MARALEUCEL (LISO‐CEL) IN THE NONUNIVERSITY SETTING

J. E. Godwin

, B. Mattar

, M. Maris

, C. Bachier

, D. A. Stevens

, D.

Hoda

, J. C. Varela

, M. Cherry

, S. Fanning

, J. Essell

, H. Yimer

, J.

Courtright

, J. Sharman

, N. S. Trede

, M. Youssef

, J. Lymp

, P.

Shaughnessy

Providence Cancer Center, Earle A. Chiles Research Institute, Oncology

Hematology Clinic, Portland, Oregon, USA,

Cancer Center of Kansas,

Internal Medicine, Wichita, Kansas, USA,

Colorado Blood and Cancer

Institute and Sarah Cannon Research Institute, Hematology/Oncology,

Denver, Colorado, USA,

Sarah Cannon Center for Blood Cancer,

Hematology, Nashville, Tennessee, USA,

Norton Healthcare, Medical

Oncology, Louisville, Kentucky, USA,

Intermountain Healthcare, Loveland

Clinic for Blood Cancer Therapy, Salt Lake City, Utah, USA,

Advent

Health , Blood and Marrow Transplant Program, Orlando, Florida, USA,

Atlantic Health System, Carol Simon Cancer Center, Morristown, New

Jersey, USA,

Prisma Health, Hematology, Greenville, South Carolina, USA,

Oncology Hematology Care, Medical Oncology, Hematology, Blood and

TABLE: MAIC of Tisa‐cel Infused vs. Liso‐cel Efﬁcacy‐evaluable Set

Tisa‐cel vs. liso‐cel (95% CI); p‐value

OS, hazard ratio (HR) 1.12 (0.62, 2.05); p =0.71;

1‐year OS rate: 55.1% vs 57.9%

PFS, HR 1.16 (0.64, 2.09); p =0.63;

1‐year PFS rate: 47.4% vs 44.1%

CR, rate difference ‐5.4% (‐15.5%, 4.7%); p =0.29

OR, rate difference ‐9.7% (‐20.0%, 0.6%); p =0.07

368

SUPPLEMENT ABSTRACTS

Marrow Transplantation, Cincinnati, Ohio, USA,

Texas Oncology‐Tyler,

Hematology, Medical Oncology, Tyler, Texas, USA,

Texas Oncology,

Medical City Dallas, Dallas, Texas, USA,

Willamette Valley Cancer

Institute, Blood Cancers, General Oncology, Eugene, Oregon, USA,

Bristol Myers Squibb, Clinical Development, Seattle, Washington, USA,

Bristol Myers Squibb, Global Drug Development, Princeton, New Jersey,

USA,

Bristol Myers Squibb, Cell Therapy Biostatistics, Seattle, Wash-

ington, USA,

Sarah Cannon Transplant and Cellular Therapy Program,

Methodist Hospital, San Antonio, Texas, USA

Introduction: Concerns about adverse event management related to

chimeric antigen receptor (CAR) T cell therapy have resulted in

administration of this therapy largely in an inpatient setting. Infusion

and monitoring of patients (pts) who receive CAR T cell therapy at

nonuniversity medical centers (NMCs) and in outpatient settings

have not been studied speciﬁcally. This study evaluated the safety

and efﬁcacy of liso‐cel in pts with relapsed/refractory (R/R) large B‐

cell lymphoma (LBCL) across inpatient and outpatient settings at

NMCs in OUTREACH (NCT03744676).

Methods: This open‐label, multicenter, phase 2 study enrolled adult

pts with R/R LBCL at NMCs, including centers naïve to CAR T cell

therapy. Eligible pts had R/R positron emission tomography‐positive

disease after ≥2 lines of prior systemic therapy, ECOG PS ≤1, and

adequate organ function. Prior autologous HSCT was permitted.

After leukapheresis and lymphodepleting chemotherapy, pts received

sequential infusions of equal target doses of CD8

and CD4

cells at

a total target dose of 100 �10

CAR

T cells. The primary endpoint

was incidence of grade ≥3 cytokine release syndrome (CRS) graded

per 2014 Lee criteria, neurological events (NEs), prolonged cytope-

nias (Day 29 grade ≥3 lab values), and infections. Secondary end-

points were safety and overall response rate (ORR). All study sites

had a multidisciplinary CAR T cell therapy team and standard oper-

ating procedures (SOPs) for toxicity monitoring/management of pts

treated and/or monitored as outpatients.

Results: At data cutoff, 46 pts (inpatients, n =16; outpatients, n =30)

were treated with liso‐cel. Median age was 63 (range, 34−83) years,

63% had diffuse LBCL not otherwise speciﬁed, and 91% were re-

fractory to last therapy. Inpatients and outpatients had similar de-

mographics and baseline disease characteristics. Safety data were

similar across the inpatient and outpatient groups (Table). Overall,

the most common treatment‐emergent adverse events were neu-

tropenia (32; 70%), leukopenia (22; 48%), and anemia (18; 39%). Early

(study Day ≤4) and overall hospitalization was reported in 27% and

63% of outpatients, respectively; median time to hospitalization was

5 (2–61) days and median length of stay was 6 (1–28) days. For

efﬁcacy‐evaluable pts (n =44), ORR was 75% for inpatients and 79%

for outpatients; complete response rates were 50% and 61%,

respectively.

Conclusions: Liso‐cel was successfully administered to pts with R/R

LBCL in the outpatient setting and pts were monitored for CAR T cell

therapy–related toxicities by multidisciplinary teams using SOPs.

Incidences of severe CRS and NEs and tocilizumab and/or cortico-

steroid use were similar in inpatients and outpatients. Data were

consistent with pivotal study observations (Abramson JS, et al. Lan-

cet. 2020;396:839‐852). Updated data with longer follow‐up will be

presented.

EA – previously submitted to EBMT, ASCO and EHA 2021.

The research was funded by: This study was funded by Juno

Therapeutics, a Bristol‐Myers Squibb Company. All authors

contributed to and approved the presentation; writing and editorial

assistance were provided by Amy Agbonbhase, PhD, of The

Lockwood Group (Stamford, CT, USA), funded by Bristol Myers

Squibb.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Cellular ther-

apies, OngoingTrials

Conﬂicts of interests pertinent to the abstract

TABLE: Adverse events of interest

SUPPLEMENT ABSTRACTS

369

B. Mattar

Employment or leadership position: Cancer Center of Kansas

Consultant or advisory role: BMS, GSK

C. Bachier

Consultant or advisory role: Juno/BMS, CRISPR, Kadmon, Autolus,

Mana Therapeutics

D. Hoda

Consultant or advisory role: Amgen

J. C. Varela

Consultant or advisory role: Nexlmmune

Stock ownership: Nexlmmune

Honoraria: Nexlmmune, Kite, Omeros

Other remuneration: Speakers Bureau: Kite

S. Fanning

Consultant or advisory role: TG Pharma, Abbvie

Other remuneration: Speakers Bureau: Takeda, BMS, Sanoﬁ

J. Essell

Other remuneration: Speakers Bureau: Kite, BMS

H. Yimer

Other remuneration: Speakers Bureau: Janssen, AZ, Takeda, Bei-

Gene, KaryoPharm

J. Sharman

Consultant or advisory role: Abbive, Astra Zeneca, BeiGene, Janssen,

Pﬁzer, Genentech, TG Therapeutics, BMS, Celgene

N. S. Trede

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

M. Youssef

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

J. Lymp

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

P. Shaughnessy

Other remuneration: Speakers Bureau: Sanoﬁ, Kite

274 |OUTCOME DETERMINANTS OF COMMERCIAL CAR‐T

CELL THERAPY FOR LARGE B‐CELL LYMPHOMA: RESULTS OF

THE GLA/DRST REAL WORLD ANALYSIS

P. Dreger

, P. Martus

, U. Holtick

, F. Ayuk

, E. M. Wagner‐Drouet

G. Wulf

, R. Marks

, O. Penack

, C. Koenecke

, M. von Bonin

, B. von

Tresckow

, M. Stelljes

, C. Baldus

, V. Vucinic

, D. Mougiakakos

, M.

Topp

, D. Wolff

, R. Schroers

, M. Schmitt

, T. Schmitt

, C. Lengerke

S. Thomas

, D. W. Beelen

, W. Bethge

German Lymphoma Alliance, Working Group Hematopoietic Cell

Therapy, Muenster, Germany,

German Registry for Stem Cell

Transplantation, DRST, Essen, Germany

Introduction: In Germany, commercial CAR‐T cell therapies are

registered with the German Registry for Stem Cell Transplantation

(DRST), which is the National partner organization of the EBMT

registry. Here, we present the ﬁrst risk factor analysis of standard‐of‐

care (SOC) CAR‐T cell therapies for large B‐cell lymphoma (LBCL)

based on DRST data.

Methods: Eligible were all patients who received SOC axi‐cel (A) or

tisa‐cel (T) for treatment of LBCL until December 2020 and were

registered with the DRST. Baseline patient, disease, and treatment

data were collected from MED‐A Cellular Therapy forms. Centers

were contacted to provide additional course and follow‐up infor-

mation. Main outcomes analyzed were toxicities, response, and sur-

vival endpoints. Predictors of progression‐free survival (PFS) were

analyzed by uni‐and multivariate comparisons.

Results: A total of 267 patients were enrolled by 18 centres (A

137, T 130). Compared to the approval trials, patients were of

relatively poor risk with 51% being ZUMA1‐ineligible, 71% pre-

senting with elevated LDH at lymphodepletion, 79% needing

bridging, and 80% having received ≥3 pretreatment lines. Whereas

A and T cohorts were comparable for age, sex, LDH, and pre-

treatment, the T group contained signiﬁcantly larger proportions of

patients with unfavorable IPI, poor performance status, and need

for bridging. Both CRS and neurotoxicity were signiﬁcantly more

common after A compared to T. 17 grade 5 toxicities occurred (A

12, T 5; ns), largely due to infections. Overall and complete

response rates to A and T were 77% and 47% (p <0.0001), and

40% and 25% (p =0.013), respectively. With a median follow‐up

of 6.7 months, progression/relapse occurred in 71 (52%) and 91

(72%) patients after A and T, respectively (p =0.0027). Of note,

17 events were observed beyond 6 months, and 3 beyond 12

months post dosing. PFS, overall survival, and non‐relapse mor-

tality (NRM) 12 months after dosing of A and T were 32% and

15% (p =0.0018), 54% and 47% (ns), and 8% and 4% (ns),

respectively. Other signiﬁcant risk factors for PFS on univariate

analysis were elevated LDH, need for bridging, and >3 pretreat-

ment lines. The adverse impact of T, LDH, and bridging on PFS

remained signiﬁcant after multivariable adjustment for confounders

(HR 1.51 (95%CI 1.12‐2.04), 1.55 (1.1‐2.18), and 1.66 (1.12‐2.46),

respectively).

Conclusion: The results of this large GLA/DRST analysis on SOC

CAR‐T cell treatment of LBCL are impaired by an abundance of

relapse and NRM events beyond the 6‐month landmark not observed

in other studies. The enrichment of poor‐risk features in our sample

might have contributed to this ﬁnding. Determinants of an adverse

outcome are elevated LDH, bridging, and use of T. The short follow‐

up and the limitations of a registry study have to be taken into

account.

370

SUPPLEMENT ABSTRACTS

Keywords: Cellular therapies, Immunotherapy

Conﬂicts of interests pertinent to the abstract

P. Dreger

Consultant or advisory role: Gilead, Novartis, BMS, bluebird bio,

Takeda

275 |FIRST REPORT OF THE REAL‐LIFE PROSPECTIVE

OBSERVATIONAL STUDY “CAR‐T CELL IN DIFFUSE LARGE B‐CELL

AND PRIMARY MEDIASTINAL LYMPHOMAS” OF THE ITALIAN

SOCIETY OF HEMATOLOGY

A. Chiappella

, A. Guidetti

, A. Dodero

, S. Bramanti

, P. Zinzani

, A.

Santoro

, B. Casadei

, A. Di Rocco

, M. Carrabba

, P. Chiusolo

, M.

Martino

, A. M. Barbui

, M. C. Tisi

, R. Miceli

, C. Carniti

, P.

Corradini

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Hematology

and Stem Cell Transplantation, Milano, Italy,

Humanitas Clinical and

Research Center, IRCCS, Hematology, Rozzano, Italy,

University of

Bologna, Institute of Hematology “Seràgnoli”, Bologna, Italy,

'Sapienza'

University of Rome, Department of Translational and Precision Medicine,

Roma, Italy,

San Raffaele Hospital, IRCCS, Hematology and Bone Marrow

Transplantation Unit, Milano, Italy,

Fondazione Policlinico Universitario

A. Gemelli IRCCS; Università Cattolica del Sacro Cuore, Department of

Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia;

Hematology Section, Department of Scienze Radiologiche ed

Ematologiche, Roma, Italy,

Grande Ospedale Metropolitano “Bianchi‐

Melacrino‐Morelli”, Stem Cell Transplant and Cellular Therapies Unit,

Reggio Calabria, Italy,

Azienda Socio Sanitaria Territoriale (ASST),

Ospedale Papa Giovanni XXIII, Hematology Unit, Bergamo, Italy,

San

Bortolo Hospital, Cell Therapy and Hematology, Vicenza, Italy,

Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano, Unit of

Clinical Epidemiology and Trial Organization; Department of Applied

Research and Technological Development, Milano, Italy,

Fondazione

IRCCS Istituto Nazionale dei Tumori, Milano, Italy, Laboratory of

Hematology, Division of Hematology and Stem Cell Transplantation,

Milano, Italy,

Chair of Hematology, University of Milano; Fondazione

IRCCS Istituto Nazionale dei Tumori di Milano, Division of Hematology

and Stem Cell Transplantation, Milano, Italy

Introduction: Axicabtagene ciloleucel (axi‐cel) and tisagenlecleucel

(tisa‐cel) are anti‐CD19 chimeric antigen receptor T cells (CAR‐T)

that proved very effective in relapsed/refractory (R/R) diffuse large

B‐cell (DLBCL) and primary mediastinal B‐cell lymphoma (PMBCL). to

evaluate safety and efﬁcacy of axi‐cel and tisa‐cel.

Methods: The Italian Society of Hematology (SIE) is conducting a

prospective observational trial aimed to: 1. register all DLBCL and

PMBCL patients (pts) candidate to CAR‐T in the Italian authorized

centers; 2. evaluate the intention to treat overall response rate (ORR,

complete [CR] and partial response [PR]), duration of response

(DOR), progression free survival (PFS) and overall survival (OS); 3.

evaluate safety in terms of cytokine release syndrome (CRS), immune

effector cell‐associated neurotoxicity syndrome (ICANS) and long‐

term cytopenia; 5. evaluate different CAR‐T products. The study

was approved by ethics committees.

Results: Since March 2019 to January 2021, 126 pts were leuka-

pheresed and 113 infused. Clinical characteristics of the 113 infused

pts were: median age 53 years (19‐70), stage III/IV 77 (68%), 81

(72%) primary refractory; median number of prior lines was 3 (2‐7),

including 33 (29%) prior autologous stem cell transplantation. For

histologies, 59 (52%) were DLBCL, 18 (16%) high‐grade B‐cell

(HGBCL), 23 (20%) PMBCL, 13 (12%) transformed Follicular (tFL).

Bridging therapy was delivered to 97 pts (86%) and all pts received

lymphodepletion. Fifty‐nine (52%) infused axi‐cel and 54 (48%) tisa‐

cel. Median follow‐up time for infused pts was 6.9 months (IQR: 3.13‐

11.78). At 30‐days after the infusion, all the pts were evaluable for

response: 45 (40%) CR, 35 (31%) PR, with ORR of 71%. For the

evaluable pts, DOR was 73% (95%CI:62‐85) at 6‐months and 58%

(95%CI:44‐77) at 12‐months. In the whole series, 6 and 12‐months

PFS were 54% (95% CI:45‐65) and 46% (95%CI:35‐59); 6 and 12‐

months OS were 80% (95%CI:71‐88) and 75% (95%CI:65‐86),

respectively. With the limitation of small number, 6‐months PFS were

48% for DLBCL, 62% for HGBCL, 66% for PMBCL and 59% for tFL;

6‐months OS by histotype were 78% for DLBCL, 80% for HGBCL,

80% for PMBCL and 92% for tFL. No differences between axi‐cel and

tisa‐cel were reported. Severe (grade 3‐4) CRS was observed in only

6 (5%) pts, and severe ICANS in 11 (10%). Sixty‐one (54%) pts

received tocilizumab and 38 (34%) steroids. Cytopenia beyond 30

days was reported in 30 (27%) pts; 27 of them (24%) experienced

viral or bacterial infections. No toxic deaths were recorded.

Conclusions: In the real‐life, axi‐cel and tisa‐cel showed an ORR

similar to those of the registrative trials, even if almost all pts un-

derwent bridging therapy. The response rate is similar across histo-

types and between products. CAR‐T toxicity is manageable, relapse

beyond 6 months is a rare event. Cytopenias as well as infections are

an emerging problem in real‐life setting.

EA – previously submitted to EHA 2021.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Cellular ther-

apies, Immunotherapy

No conﬂicts of interests pertinent to the abstract.

276 |FDG‐PET IMAGING AND RADIOMICS IN RESPONSE

ASSESSMENT OF LYMPHOMA PATIENTS UNDERGOING CAR T‐

CELL THERAPY

B. Casadei

, A. Paccagnella

, A. Farolﬁ

, L. Argnani

, C. Malizia

, G.

Paolani

, M. Santoro

, G. Della Gala

, S. Strolin

, L. Strigari

, S.

Guadagnuolo

, F. Bonifazi

, S. Fanti

, P. L. Zinzani

IRCCS Azienda Ospedaliero‐Universitaria di Bologna Istituto di Emato-

logia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diagnostica

e Sperimentale Università di Bologna, n/a, Bologna, Italy,

IRCCS Azienda

Ospedaliero‐Universitaria di Bologna, Nuclear Medicine Unit, Bologna,

Italy,

IRCCS Azienda Ospedaliera Universitaria Bologna, Medical Physics

SUPPLEMENT ABSTRACTS

371

Department , Bologna, Italy,

IRCCS Azienda Ospedaliera Universitaria

Bologna, Hematology, Bologna, Italy

Background: Radiomics involves the extraction of quantitative fea-

tures from medical images, such as positron emission tomography

(PET), representing potential surrogate markers of the lymphoma

phenotypes. Chimeric antigen receptor‐T (CAR‐T) cell therapy has

revolutionized the treatment of large B cell lymphomas. Unfortunately,

the relapse rate is around 30–60% and almost 20% of patients develop

grade >3 Cytokine Release Syndrome (CRS). In this setting, it is of

critical importance the early identiﬁcation of relapsed/refractory pa-

tients and of whom can develop CRS. Primary aim was to early predict

the response to CAR‐T based on metabolic features extracted from the

clinical and baseline FDG‐PET. Secondary aim was to determine the

presence of CRS from the clinical and image‐based features.

Methods: From September 2019 to December 2020, 20 patients

were treated with CAR T‐cell therapy. All patients underwent FDG‐

PET/CT evaluation at baseline (PET_0) and 1 month after (PET_1)

CAR T‐cell infusion. PET_0 semi‐quantitative parameters, namely

SUVmax, metabolic tumor volume (MTV), total lesion glycolysis

(TLG), were calculated. Pyradiomics library was used for the extrac-

tion of 105 radiomics features from each image. Univariate analysis

on both clinical and radiomics features was performed to evaluate

the correlation with the outcome. A generalized linear model (GLM)

was trained to predict the outcome and ROC analysis was used to

assess the prediction capability.

Results: Patients had a wide range of baseline disease burden, with a

median MTV of 129 ml (range: 5‐5916) and a median TLG of 971 Bq

(range: 21‐32241). Ten (53%) patients achieved a complete (CR) and

9 (47%) a partial response (PR). Of these 9 patients, 6 underwent re‐

evaluation at 3 months: 1 converted to CR, 4 had a progression to

PD and 1 patient maintained the PR. No correlation was found be-

tween baseline MTV and TLG and tumor response at PET_1, while

they were signiﬁcantly associated with the severity of CRS (p <0.5)

(AUC: 0.95; 95%CI: 0.87‐1 for MTV and AUC: 0.92; 95%CI: 0.79‐1

for TLG). Two radiomics features, Kurtosis and Median, were sta-

tistically signiﬁcantly correlated with response at PET_1, while the

surface area was statistically signiﬁcantly correlated with moderate/

severe CRS. In the GLM, only Median was a prognostic factor of

response, with an AUC of 0.81 (p <0.002) while surface area was a

prognostic factor of moderate/severe CRS with an AUC of 0.81 (p <

0.009).

Conclusions: Baseline FDG‐PET radiomics features were able to

differentiate between early responder and non‐responder patients

treated with CAR‐T and between patients with/without moderate/

severe CRS; MTV and TLG were also associated with CRS. Further

correlation between FDG‐PET_0 radiomics features/clinical baseline

characteristics and patients’ outcome (including progression free

survival) will be investigated with larger cohort and longer follow‐up.

Keywords: Diagnostic and Prognostic Biomarkers, PET‐CT, Cellular

therapies

No conﬂicts of interests pertinent to the abstract.

277 |QUANTITATIVE METABOLIC PARAMETERS

EVALUATION IN PATIENTS WITH AGGRESSIVE B‐CELL

LYMPHOMAS TREATED WITH ANTI‐CD19 CAR T‐CELLS

A. Guidetti

, A. Dodero

, G. Argirofﬁ

, P. Verderio

, A. Lorenzoni

, A.

Chiappella

, C. Carniti

, E. Seregni

, s. Pizzamiglio

, A. Alessi

, P.

Corradini

Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology, Milano,

Italy,

Fondazione IRCCS Istituto dei Tumori, Nuclear Medicine, Milano,

Italy,

Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of

Bioinformatics and Biostatistics, Milano, Italy

Introduction: Autologous anti‐CD19 chimeric antigen receptor (CAR)

T‐cell therapy is an effective therapy for relapsed/refractory (R/R)

aggressive B‐cell lymphomas and predictive biomarkers of response

are required. Quantitative metabolic parameters from 18‐FDG PET‐

CT scan are emerging tools able to predict outcome in aggressive

lymphomas, but their value in the CAR T setting is still under

investigation.

Methods: We conducted an observational prospective study of 34

patients affected by R/R aggressive lymphomas receiving axicabta-

gene ciloeucel (axi‐cel) or tisagenlecleucel (tisa‐cel); PET‐CT was

evaluated before lymphodepletion, at 1 and 3 months post infusion.

Quantitative PET parameters were computed with PET‐VCAR

software (GE Healthcare) on dedicated workstations. Contours of

pathological lesions were delineated using two semiautomatic con-

touring system including percentage threshold of standardized up-

take value (SUVmax) (41%) and gradient based threshold (adaptive

iterative algorithm). SUVmax, SUVmean, Metabolic tumor volume

(MTV) and Total lesions glycolysis (TLG) were automatically recor-

ded. Total MTV (TMTV) and total TLG (TTLG) were calculated as

the sum of all individual lesions. A quantitative measure of intra-

tumoral heterogeneity (heterogeneity index, HI, SUVmax/SUVmean)

was also recorded. The goals were to determine whether PET‐CT

quantitative metabolic parameters could predict clinical response

as well as to explore the prognostic role of the early PET‐CT. To

these end univariate logistic and Cox regression models were

implemented.

Results: 34 patients were enrolled: 29 were evaluable, 5 were not

included in the analysis for extranodal localization of disease (bone).

Median age was 51 (range, 22‐70), 20 patients were affected by

diffuse‐large B‐cell lymphomas and 9 by primary mediastinal B‐cell

lymphoma. Patients received treatment with axi‐cel (n =18) or

tisa‐cel (n =11) at physician discretion. Before infusion, 45% had high

LDH and 38% had bulky disease. At a median follow‐up of 343 days

(IQR, 214‐482 days), 24 patients are alive and 5 died of disease

progression with an estimated PFS and OS of 39% (95%CI, 20%‐58%)

and 78% (95%CI, 55%‐91%), respectively. Clinical response at 1

month occurred in 55% of the patients (n =8 CR, n =8 PR); pro-

gressive disease at 3 months occurred in 1 pt in CR and in 4 in PR.

Baseline values of SUVmax, SUVmean, TTLG, TMTV, HI did not

correlate with clinical response and PFS. On the contrary, the

decrease of HI between baseline and 1 month were signiﬁcantly

372

SUPPLEMENT ABSTRACTS

associated with response at 1 month (OddsRatio: 1.41; 95%CI: 1.02‐

1.93; p =0.035).

Conclusions: Baseline quantitative parameters did not correlate with

outcome suggesting that several others factors could inﬂuence the

response to CAR T‐cells. The variation of metabolic heterogeneity

are strictly associated with response suggesting an important role of

early evaluation of disease after CAR T‐cells infusion. A larger cohort

of patients and a validation group are needed in order to verify these

observations.

Keywords: PET‐CT

No conﬂicts of interests pertinent to the abstract.

278 |RESISTANCE OF B‐CELL LYMPHOMAS TO CAR‐T CELL

THERAPY IS ASSOCIATED WITH HISTOPHENOTYPICAL AND

GENOMIC TUMOR CHANGES WHICH CAN INDUCE PROFOUND

TRANS‐DIFFERENTIATION

C. Laurent

, M. Hamon

, C. Syrykh

, J. Adélaïde

, A. Guille

, M.

Parrens

, P. Dartigues

, A. Bardet

, L. Mescam

, J.‐M. Schiano De

Colella

, P. Sujobert

, C. Besson

, D. Birnbaum

, L. Xerri

Oncopole, Pathology, Toulouse, France,

Hopital André Mignot,

Pathology, Versailles, France,

Oncopole, pathology, Toulouse, France,

IPC, Predictive Oncology/ CRCM, Inserm, CNRS , AMU, Marseille, France,

CRCM, Predictive oncology, Marseille, France,

Hopital haut‐Lévéque,

Pathology, Bordeaux, France,

IGR, Pathology, Villejuif, France,

Institut

Paoli‐Calmettes, pathology, Marseille, France,

CHU Lyon‐Sud, Hématol-

ogy, Pierre‐Bénite, France

Backgroud: Chimeric Antigen Receptor (CAR) T‐cell therapy target-

ing CD19 has shown efﬁcacy against B‐cell lymphomas, but a sig-

niﬁcant proportion of patients will eventually relapse. The

histopathological and molecular changes associated with treatment

failure are still largely unknown.

Methods: To clarify this point, we have analyzed 16 sequential tumor

samples from 6 patients (pts) prior CAR‐T therapy (Pre‐CAR) and at

relapse (Post‐CAR), using immunohistochemistry (IHC), FISH, array‐

CGH (CGH), Large Panel Next Generation Sequencing (NGS), RNA

sequencing (RNA seq) and genome–scale DNA methylation (METH).

Results: The initial diagnosis was diffuse large B‐cell lymphoma

(DLBCL, n =5) and Burkitt's lymphoma (BL, n =1). In 3/6 pts

(DLBCLs), the morphological, phenotypical and FISH patterns

remained mostly similar in paired sequential samples, except for a

slight decrease in CD19 staining whereas CD20, CD79A and PAX5

remained unchanged. These 3 cases exhibited isolated rearrange-

ments of BCL2,BCL6 and MYC, respectively. CGH showed an increase

in the number of chromosomal alterations in Post‐CAR. NGS showed

the occurrence of additional pathogenic variants in Post‐CAR,

including the PI3K pathway (PIK3R1, PIK3R2, PIK3C2G) and genes

associated with aggressive tumor behavior (INPP4B, SYNE1,

TBL1XR1).

In contrast, the 3 remaining cases (2 DLBCLs and 1 BL) showed

loss or drastic decrease of most B‐cell markers including CD19,

CD20, CD79A and PAX5. In 2 cases, the relapse samples displayed a

complete morpho‐phenotypic shift, with emergence of T‐cell markers

(CD2, CD3 and CD7) in 1 case; or expression of histiocytic markers

(CD163, CD68) together with a histiocyte‐like morphology in the

other case. Clonality analysis showed identical clonal IGH rear-

rangements in sequential samples from both cases. NGS showed the

occurrence of KRAS,MAP2K1 and SF3B1 mutations in Post‐CAR. A

PAX5 mutation was detected in the Post‐CAR sample with aberrant

T‐cell phenotype, which also showed reduced mRNA expression of

most B‐cell genes and increased methylation of the corresponding

promoters.

Conclusions: These preliminary results indicate that CAR‐T resis-

tance in B‐NHLs can be associated with profound dysregulation of B‐

cell differentiation and upregulation of genes involved in tumor

proliferation. The occurrence of mutations in the PI3K and KRAS

pathways suggests that appropriate targeted therapies could be

useful in CAR‐T resistant pts. Post‐CAR aberrant T‐cell phenotype

brings a proof of concept of in vivo trans‐differentiation from B‐cell

into T‐cell lymphoma program due to therapeutical selection pres-

sure. Pathologists have to be aware of such unexpected features as

potential diagnostic pitfalls.

Keywords: Pathology and Classiﬁcation of Lymphomas

No conﬂicts of interests pertinent to the abstract.

279 |IN VITRO ANALYSIS PREDICTS CLINICAL RESPONSE OF B

CELL LYMPHATIC MALIGNANCIES TO CD19 CAR‐T CELLS:

PHENOTYPIC, TRANSCRIPTIONAL AND FUNCTIONAL STUDY

K. Beider

, M. J. Besser

, E. Jacoby

, J. Schachter

, V. Voevoda‐

Dimenshtein

, E. Rosenberg

, O. Ostrovsky

, I. Danylesko

, A. Shi-

moni

, A. Avigdor

, A. Nagler

Sheba Medical Center, Hematology Division, Ramat Gan, Israel,

Sheba

Medical Center, Ella Institute of Immuno‐Oncology, Ramat Gan, Israel,

Sheba Medical Center, Department of Pediatrics, The Edmond and Lily

Safra Children's Hospital, Ramat Gan, Israel,

Sheba Medical Center, Ella

Institute of Immuno‐Oncology, Ramat Gan, Israel

In spite of high rates of overall response to chimeric antigen receptor

(CAR) T cell therapy its curative potential is jeopardized by exhaus-

tion of the CAR T cells conceivably mediated by the immunosup-

pressive tumor microenvironment and excessive antigen exposure.

However, cellular and molecular predictors of clinical response are

not fully elucidated.

We performed immunophenotypic and transcriptomic analysis

of T cells from patients (pts) with relapsed/refractory B cell ma-

lignancies (n‐39: NHL‐28, ALL‐5, CLL‐6) treated with locally pro-

duced CD19 CAR T cells in correlation with pts’ day 28 clinical

response. Intact CD3

T cells from peripheral blood (PB) samples

SUPPLEMENT ABSTRACTS

373

pre Flu/Cy lymphodepletion and the manufactured CAR T cells

were analyzed. The CD8

and CD4

T cells were individually

assessed by a panel of 17 immune surface markers identifying

different T cell subsets. Transcriptional signature was assessed by

NanoString technology.

Phenotypic signature identiﬁed a higher proportion of exhausted

CD57

CD39

cytotoxic CD8

cells in CAR T products of non‐

responders (NR) in comparison to pts with complete response (CR).

Furthermore, CD8

CAR T cells of NR were characterized by CD28

and IL‐7R loss, and lower levels of CCR7. Expression of T cell

checkpoint inhibitor PD1 was high in exhausted CD8

cells. Impor-

tantly, higher proportion of exhausted cytotoxic CD8

cells was

detected in PB of NR comparing to CR pts, suggesting the association

of CAR T exhaustion with a dysfunctional phenotype of pts’ T cells. In

contrast CD4

cells demonstrated low frequency of exhausted

phenotype both in the PB as well as the CAR T product from both NR

and CR pts achieving CR, indicating that CD4

T cells are less prone

to exhaustion suggesting better persistence of CD4 CAR T cells

following antigen exposure.

The transcriptional signature of the CAR T products overlaid

with the phenotypic characterization. Higher levels of IL‐7R, CD7,

BATF3, IL15, FOS, MYC, CD69 and CD27 genes were detected in

CAR T cells of CR pts. In contrast, CAR T cells from NR were enriched

with terminally exhausted population, upregulating CD57, TOX,

EOMES, GZMB, GZMA, GZMH, CCL4 and LAG3 genes.

Finally, the functional capacity of the CAR T cells was

evaluated in co‐culture experiments with CD19

Raji cells. Stim-

ulation with CD19

targets induced proliferation and cytokine

secretion in the CAR T effectors. Importantly, reduction of both

proliferation as well as IL‐2 secretion correlated with the

exhaustion signature.

Overall, these results reveal potential cellular and molecular

mediators of resistance, identifying an enrichment of terminally

exhausted CD8+T cells as a main feature observed in PB and CAR T

products of resistant pts. Delineating these mechanisms may guide

future T cells engineering studies to enhance the efﬁcacy and dura-

bility of CAR T therapy in B cell malignancies.

Keywords: Diagnostic and Prognostic Biomarkers

No conﬂicts of interests pertinent to the abstract.

MISCELLANEOUS

280 |GENDER DISPARITIES IN QUALITY OF LIFE OF FRENCH

PATIENTS ONE YEAR AFTER THE DIAGNOSIS OF LYMPHOMA. A

LYSA STUDY

A.‐C. Paunescu

, J. Paget

, C. Copie Bergman

, S. Malak

, S. Le

Gouill

, V. Ribrag

, K. Bouabdallah

, D. Sibon

, G. Rumpold

, M.

Preau

, N. Mounier

, C. Haioun

, F. Jardin

, C. Besson

FIGURE 1 (A) Exhausted phenotype of infused CAR T products and peripheral blood samples prior to lymphodepletion. NR non

responders (n =15), CR‐complete responders (n =24). (B) Transcriptional signature of infused CAR T products, NR and CR, analyzed by

NanoString platform. (C) Proliferation of CD8+CAR T cells upon stimulation with CD19+target cells(Raji) oppositely correlates with CD8+

exhaustion and directly correlates with interleukin‐2(IL‐2) secretion.

374

SUPPLEMENT ABSTRACTS

Gustave Roussy, Epidemiology, Villejuif, France,

Lysarc, Lysarc, Lyon,

France,

CHU Mondor, pathology, Créteil, France,

Curie, Hematology,

Saint‐Cloud, France,

CHU Nantes, Hematology, Nantes, France,

Gustave Roussy, Hematology, Villejuif, France,

CHU Bordeaux, Hema-

tology, Bordeaux, France,

CHU Necker, Hematology, Paris, France,

Medical University Innsbruck, Department of Medical Psychology, Inns-

bruck, Austria,

Université Lyon 2, GRePS, Lyon, France,

CHU Nice,

Hematology, Nice, France,

Henri Mondor University Hospital,

Lymphoid malignancies unit, Créteil, France,

Centre Henri Becquerel,

Hematology, Rouen, France,

CH Versailles, Hematology, Le Chesnay,

France

In France, Diffuse Large B‐Cell Lymphoma (DLBCL) is the most

common subtype of non‐Hodgkin lymphoma (NHL). Health‐related

quality of life (HRQoL) is a multi‐dimensional concept including

physical, emotional, social functions, disease symptoms and side ef-

fects of treatments. Differences in HRQoL due to gender are little

explored in NHL. To investigate whether differences in HRQoL be-

tween women and men exist after diagnosis of their lymphoma, we

evaluated several facets of HRQoL.

One year after DLBCL diagnosis, 141 patients, enrolled in the

RT3 (Real Time Tailored Therapy) Study in 2018 and 2019, were

invited to answer self‐administrated European Organization for

Research and Treatment of Cancer Quality of Life Questionnaire

Core 30 (EORTC QLQ‐C30), Hospital Anxiety and Depression Scale

(HADS), and Post Traumatic Growth Inventory (PTGI) questionnaires.

Adjusted means and their 95% conﬁdence intervals (95% CI) were

calculated in multivariate linear regression models, and compared

between female and male survivors.

68% of eligible patients agreed to participate and 82% of them

answered all questionnaires. Participants and non participants did

not differ signiﬁcantly regarding socio‐demographic and clinical var-

iables, as did female and male participants (mean age of 58.5 years).

The adjusted means of the EORTC QLQ‐C30 subscales were not

different between women and men, excepting for insomnia, signiﬁ-

cantly higher in women than in men (38.3 vs. 17.2, P=0.04). Anxiety

scores of HADS and several subscales of PTGI were signiﬁcantly

higher in women compared to men (Table).

Women seem to be more prone to anxiety, insomnia, and a post

traumatic growth after DLBCL than men. The explanation of these

disparities is unclear. Speciﬁc qualitative approaches should be set up

for women with DLBCL.

The research was funded by: Calym

Keywords: Cancer Health Disparities

No conﬂicts of interests pertinent to the abstract.

281 |CARDIOTOXICITY RISK IN PATIENTS WITH NON‐

HODGKIN LYMPHOMA RECEIVING EPOCH AFTER PRIOR

ANTHRACYCLINE EXPOSURE

M. J. Buege

, P. H. Dao

, E. Drill

, S. M. Horwitz

, A. LeVoir

, T. Pak

T. J. Peterson

, M. J. Matasar

Memorial Sloan Kettering Cancer Center, Pharmacy, New York, USA,

Memorial Sloan Kettering Cancer Center, Epidemiology & Biostatistics,

New York, USA,

Memorial Sloan Kettering Cancer Center, Medicine, New

York, USA

Introduction: Anthracyclines are utilized in many chemotherapy reg-

imens for lymphoma and carry a dose‐related risk of cardiotoxicity.

Reducing peak cardiomyocyte anthracycline concentrations with

continuous infusion strategies reduces the risk of cardiotoxicity. The

infusional chemotherapy regimen EPOCH (etoposide, prednisone,

vincristine, cyclophosphamide, and doxorubicin) is frequently used in

both front‐line and relapsed/refractory settings for aggressive non‐

Comparisons of psychometric scales to gender after DCBCL

SUPPLEMENT ABSTRACTS

375

Hodgkin lymphomas (NHLs). Whether through treatment for previous

malignancies or prior lines of treatment for lymphoma, a subset of

patients with NHL who receive EPOCH have had prior exposure to

bolus anthracycline regimens. Cardiac outcomes in patients who

receive EPOCH following previous anthracycline exposure remain

largely unexplored.

Methods: We reviewed adults treated for NHL with EPOCH, with or

without rituximab, at Memorial Sloan Kettering Cancer Center be-

tween 2004 and 2019 who had anthracycline exposure prior to

EPOCH. Patients who had a clinical diagnosis of heart failure at

initiation of EPOCH or did not have baseline evaluation of left ven-

tricular ejection fraction (LVEF) within 3 months prior to initiating

EPOCH were excluded. The primary outcome was incidence of

composite cardiac events consisting of LV dysfunction, heart failure,

arrhythmia, or cardiac death.

Results: Among 140 eligible patients (Table 1), the median age was

58 years; the most common diagnosis was diffuse large B‐cell lym-

phoma (79%). Inclusive of EPOCH, patients received a cumulative

median doxorubicin‐equivalent dose of 364mg/m

(Shankar SM,

et al. Pediatrics. 2008;121:e387‐96), and exposure was ≥400mg/m

in 42%. Six patients (4%) had exposure to dexrazoxane at any time.

Median time between initiation of EPOCH and the most recent

available evaluation of LVEF was 2 months (range, 0 to 140 months).

At median follow‐up from initiation of EPOCH of 36 months, 23

cardiac events were noted in 20 (14%) patients. Cumulative inci-

dence of cardiac events limited to LV dysfunction or heart failure

was 9% at 120 months, with most events occurring after the ﬁrst

year (Figure 1). Risk factor analysis, including impact of cumulative

anthracycline dose and characteristics associated with risk of cardiac

events, is underway and will be included in the ﬁnal presentation.

Conclusions: In this cohort, which represents the largest experience

with EPOCH chemotherapy following prior bolus anthracycline, cu-

mulative incidence of cardiac events was low. Cumulative incidence

of LV dysfunction or heart failure was particularly low, suggesting

infusional anthracycline administration may mitigate risk despite

TABLE 1*(n =140)‐Sample characteristics and cardiac outcomes

FIGURE 1 Cumulative incidence of cardiac events

376

SUPPLEMENT ABSTRACTS

prior exposure. Risk may be underestimated due to limited duration

of LVEF monitoring after EPOCH initiation, although the low rate of

clinically evident cardiac events supports the safety of EPOCH

despite prior bolus anthracycline therapy.

Keywords: Late Effects in Lymphoma Survivors, Aggressive B‐cell

non‐Hodgkin lymphoma, Aggressive T‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

S. M. Horwitz

Consultant or advisory role: ADCT Therapeutics, Aileron, Corvus,

Forty‐Seven, Innate Pharma, Kyowa‐Hakka‐Kirin, Millenium/Takeda,

Mundipharma, Portola, Seattle Genetics

Research funding: ADCT Therapeutics, Aileron, Celgene, Forty‐

Seven, Inﬁnity/Verastem, Kyowa‐Hakka‐Kirin, Millenium/Takeda,

Seattle Genetics, Trillium

M. J. Matasar

Consultant or advisory role: Genentech, Bayer, Merck, Juno, Roche,

Teva, Rocket Medical, Seattle Genetics

Honoraria: Genentech, Roche, Bayer, Pharmacyclics, Janssen, Seattle

Genetics, GlaxoSmithKline

Research funding: Genentech, Roche, GlaxoSmithKline, Bayer, Phar-

macyclics, Janssen, Rocket Medical, Seattle Genetics

Educational grants: Genentech, Roche, Seattle Genetics, Bayer

282 |BURDEN OF LYMPHOMA IN CHINA, 1990−2019: AN

ANALYSIS OF GLOBAL BURDEN OF DISEASES, INJURIES, AND

RISK FACTORS STUDY 2019

W. Liu

, J. Liu

, Y. Song

, X. Wang

, L. Mi

, C. Cai

, D. Zhao

, L. Wang

J. Ma

, J. Zhu

Peking University Cancer Hospital & Institute, Department of Lymphoma,

Beijing, China,

National Center for Chronic and Noncommunicable

Disease Control and Prevention, Chinese Center for Disease Control and

Prevention, National Center for Chronic and Noncommunicable Disease

Control and Prevention, Beijing, China,

Beijing Institute of Survey and

Mapping, Beijing Municipal Key Laboratory of Urban Spatial Information

Engineering, Beijing Institute of Survey and Mapping, Beijing, China,

Harbin Institute of Hematology & Oncology, Harbin Institute of

Hematology & Oncology, Harbin, China

Background: China is facing the aggravating disease burden of lym-

phoma. However, the accurate information about lymphoma burden

at national and provincial levels is limited.

Methods: Following the general analytical strategy used in

Global Burden of Diseases, Injuries, and Risk Factors Study 2019,

the age‐, sex‐and province‐speciﬁc incidence, mortality and preva-

lence of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL)

were analyzed. Lymphoma burden was assessed by methods of

incidence, mortality, prevalence and disability‐adjusted life years

(DALYs).

Results: The estimated number and age‐standardized rates of DALYs

per 100,000 population were 86,171.85 and 4.95 for HL, and

1,306,247.77 and 71.00 for NHL, respectively. There were estimated

9,470 new cases and 2,710 deaths of HL, and 91,950 new cases and

44,310 deaths of NHL. Older individuals had higher lymphoma burden

with a peak of the age‐speciﬁc DALYs rates reached at the age group

70‐74 for both HL and NHL. The age‐standardized DALYs rates in

males was about 2 folds higher than that in females. Moreover, dis-

parities in lymphoma burden was observed across provinces. Between

1990 and 2019, the burden of HL kept a downward trend with a

decrease of 57.8% in the DALY number and 74.4% in the age‐

standardized DALYs rates, while the burden of NHL aggravated with

an increase of 100.9% in the DALY number and 15.6% in the age‐

standardized DALYs rates.

Conclusion: Burden of lymphoma showed heterogeneous change

pattern varied by sex, age, and provinces, with a steady improvement

for HL and a ﬂuctuant change for NHL.

Keywords: Hodgkin lymphoma, Non‐Hodgkin (Pediatric, Adolescent,

and Young Adult)

No conﬂicts of interests pertinent to the abstract.

283 |IMPACT OF THE COVID‐19 PANDEMIC ON THE

DIAGNOSIS OF MATURE LYMPHOID NEOPLASMS IN BELGIUM:

RESULTS FROM THE BELGIAN CANCER REGISTRY

H. Antoine‐Poirel

, F. Calay

, T. Tambuyzer

, P. Denolf

, L. Van

Eycken

Belgian Cancer Registry, BCR, Brussels, Belgium

Introduction: Health care in Belgium was affected by the corona

pandemic and the corresponding measures taken by the govern-

ment since March 2020. The aim of this study is to make an esti-

mate of the decrease in the number of new diagnoses of

mature lymphoid neoplasms (MLN) due to the COVID‐19 crisis in

Belgium.

Methods: For its standard cancer reporting, the Belgian Cancer

Registry uses two data sources:

• The oncological care programs from the hospitals provide

structured data (‘clinical network’)

• The pathology laboratories deliver structured ﬁles and reports

(‘pathology network’)

Thanks to expedited deliveries of data by the pathology network

between January and September 2020, the Belgian Cancer Registry

was able to make an estimation of the decline in the number of di-

agnoses by types of MLN.

Since estimates were only based on pathology data and to pre-

vent bias, all results are shown as a relative ratio between the new

cancer diagnoses for incidence years 2020 and 2019. The ratios for

the months January and February, both prior to the start of the

COVID‐19 pandemic, were expected to be around 100%. Decline =

ratio ‐100%.

SUPPLEMENT ABSTRACTS

377

Results: After a strong decline by 28% during the ﬁrst wave (March‐

May 2020) when compared to March‐May 2019, the total diagnosis

of MLN reported by the pathology network stabilized around normal

values compared to 2019 levels, leading to an incomplete recovery

by end September 2020 (‐12%).

Variable effect by age group

Although the 2 adult age groups, 20‐79 vs 80+, exhibited the

same reduction of 28% during the March‐May period, a partial re-

covery was observed for the 20‐79 age group (+4%) during the

following June‐September period while the older population showed

a persistent reduction (‐9%), leading to an overall decline of 16% for

the 80+compared to 10% for the 20‐79 age group.

Although subject to a low number of cases, there was no evi-

dence of a decline in children and adolescents up to 19 years of age.

Variable effect by MLN type

Among B‐cell MLN, the largest decrease by September was

observed for mature B‐cell leukemias (March‐Sept: ‐28%; March‐

May: ‐43%). The decrease was smaller for plasma cell neoplasms

(‐18%; ‐34%), other indolent lymphomas (‐14%; ‐40%) and Hodgkin

lymphoma (‐6%; ‐30%) while no evidence of decline for the more

aggressive MLN (DLBCL and Burkitt lymphoma), except for 80+

(March‐Sept: ‐13%).

The strongest rebound in diagnosis was observed for mature T/

NK cell lymphomas which completely recovered to above 2019 levels

(March‐May: ‐22%, June‐Sept: +25%).

Conclusion: This study with pathology data available until the end of

September suggests a heterogeneous impact of the COVID19 crisis

on the different types of MLN. The largest persistent declines are

observed for the more indolent MLNs, while the effect was very

limited for the high‐grade B‐cell lymphoid neoplasms, with exception

of the older population.

The impact over the whole year 2020 will be presented during

the meeting.

The research was funded by: Belgian Fondation Against Cancer

Keywords: Cancer Health Disparities, Pathology and Classiﬁcation of

Lymphomas

No conﬂicts of interests pertinent to the abstract.

284 |IMPAIRED HUMORAL RESPONSE IN LYMPHOMA

PATIENTS SURVIVING THE ACUTE PHASE OF COVID‐19

C. Cattaneo

, V. Cancelli

, C. Pagani

, A. Ogna

, A. Tucci

, G. Rossi

V. Quaresima

, A. Sotttini

, K. Dobbs

, L. D. Notarangelo

, J. I.

Cohen

, P. D. Burbelo

ASST‐Spedali Civili, Hematology, Brescia, Italy,

CREA (Centro Ricerca

AIL), ASST Spedali Civili di Brescia, Diagnostic Department, Brescia, Italy,

National Institute of Allergy and Infectious Diseases, National Institutes

of Health, Laboratory of Clinical Immunology and Microbiology, Bethesda,

Maryland, USA,

National Institute of Allergy and Infectious Diseases,

National Institutes of Health, Laboratory of Infectious Diseases, Bethesda,

Maryland, USA,

National Institutes of Health, National Institute of Dental

and Craniofacial Research, Bethesda, Maryland, USA

Introduction: The ability to generate an adequate and durable im-

mune response to SARS‐CoV‐2 in B‐cell lymphoma patients (pts)

treated with immunochemotherapy is still unclear. We monitored

378

SUPPLEMENT ABSTRACTS

antibody levels during convalescence in COVID‐19 survivors with

lymphoma, compared to other hematologic diseases (HemD) and

healthy controls (Ctrls).

Methods: Seventeen pts with non‐Hodgkin lymphoma (NHL) [follic-

ular (FL): 9; diffuse large B‐cell (DLBCL): 8] surviving the acute phase of

virologic‐proven COVID‐19 were evaluated at 3 timepoints (TP) after

nasal swab negativity: +1 (TP1), +3 (TP3), and +6 (TP6) months; 28 pts

affected by HemD (10 multiple myeloma, 8 chronic lymphoprolifer-

ative disorders, 10 myelodysplastic/chronic myeloproliferative syn-

dromes) and 17 Ctrls were also evaluated at the same TP. Antibody

(Ab) levels to nucleocapsid (N‐Ab) and spike (S‐Ab) virus proteins were

measured using a highly sensitive luciferase‐immunoprecipitation

system (LIPS) assay. Positive levels were 125000 LU for N‐Ab and

45000 LU for S‐Ab.

Results: Mean N‐and S‐Ab levels were lower in FL and DLBCL than in

other HemD pts, both at TP1 (N‐Ab 1217517 vs 2205610 LU, p =0.03;

S‐Ab 580444 vs 1184453 LU, p =0.049) and at TP3 (N‐Ab 850510 vs

2094487 LU p =0.012, S‐Ab 605284 vs 1230946 LU, p =0.074). At

TP6 N‐Ab levels declined in all subgroups, while S‐Ab levels remained

stable. At TP1, compared to HemD, signiﬁcantly less FL and DLCBL pts

reached positive levels of N‐Ab (93% vs 59% p =0.017) and of S‐Ab

(86% vs 47%; P: 0.008). Positive levels of N‐Ab and S‐Ab were also

more frequent in Ctrls (100% and 87%; p =0.007 and 0.028) than in

NHL pts. Rates of seroprotection remained lower in NHL pts also at

TP3 and TP6. Rituximab (RTX) had been given to 14/17 NHL pts, either

≥6 months in 5 (prior RTX) or <6 months in 9 pts (ongoing RTX) before

Covid‐19 diagnosis. Ongoing RTX had a markedly negative effect on S‐

Ab levels since none of 9 patients seroconverted at TP1 compared to 5/

5 prior RTX pts (P =0.0005). No changes occurred in the rate of

seroprotected pts also at TP3 and TP6 except for 1 ongoing RTX pt who

reached protective levels at TP6 (see ﬁgure). Overall seroprotective Ab

at any TP were present in 2 of 18 determinations in ongoing RTX pts,

despite RTX treatment discontinuation, and in 15 of 15 determination

in prior RTX pts (p =0.0001).

Conclusions: In FL and DLC NHL pts the humoral immune response to

SARS‐Cov2 is less effective than in other HemD and in Ctrls. However,

in seroconverted pts, S‐Ab levels did not signiﬁcantly decrease after 6

months. Ongoing RTX at Covid‐19 was detrimental in that it did not

allow to develop a humoral anti‐S immune response and lack of

seroconversion persisted in most pts long‐term despite discontinuing

RTX. These data could be considered with regard to vaccination policy,

although larger studies are needed to conﬁrm them.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Indolent non‐

Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

285 |MULTICENTER RETROSPECTIVE ANALYSIS OF RISK

FACTORS FOR MORTALITY OF COVID‐19 INFECTION IN

PATIENTS WITH LYMPHOMA

J. Kořen

, K. Steinerová

, A. Janíková

, D. Belada

, B. Hájková

, M.

Krčméryová

, V. Hanáčková

, B. Vacková

, P. Jindra

, M. Osovská

, E.

Svobodová

, L. Dlouhá

, P. Vodička

, M. Trněný

1st Department of Medicine, Faculty of Medicine 1, Charles University,

General Hospital, Prague, Czech Republic, haematology, Prague, Czech

Republic,

Department of Haematology and Oncology, Charles University

Hospital Pilsen, Czech Republic, haematology anf oncology, Pilsen, Czech

Republic,

3Department of Internal Medicine, Hematology and Oncology,

University Hospital Brno and Faculty of Medicine, Masaryk University

Brno, Brno, Czech Republic, Hematology and Oncology, Brno, Czech

Republic,

4th Department of Internal Medicine ‐Haematology, Charles

University, Hospital and Faculty of Medicine, Hradec Králové, Czech

Republic, haematology, Hradec Králové, Czech Republic,

Department of

Haematooncology, University Hospital Ostrava, Czech Republic,

haematology, Ostrava, Czech Republic,

1Internal Clinic of Hematology,

University Hospital Kralovske Vinohrady, Third Faculty of Medicine,

Charles University in Prague, Czech Republic, haematology, Prague, Czech

Republic,

Department of Hemato‐Oncology, Faculty of Medicine, Palacky

University and University Hospital Olomouc, Czech Republic, haematol-

ogy, Olomouc, Czech Republic

Covid 19 infection leads to signiﬁcantly higher morbidity and mor-

tality among lymphoma patients (pts.) compared to immunocompe-

tent population. The majority of published data is based on the

cohorts diagnosed during the spring and early autumn 2020 Covid‐

19 outbreak. Here we present a retrospective analysis of mortality

SUPPLEMENT ABSTRACTS

379

data and risk factors in one of the largest groups of pts. with lym-

phomas described so far, with majority diagnosed in the second half

of 2020 and early 2021.

Patients and methods. A total of 360 pts. followed for lymphoma

and participated in NiHiL project in 7 centers in the Czech Republic

and with COVID‐19 diagnosis during the period from February 2020

to February 26 2021 were included. The lymphoma and COVID‐19

characteristics were analysed and descriptive stastistic were used.

The median age of the whole group was 65 years (19‐89), 58% of

them were men, and 55% pts were on the antilymphoma therapy. In

terms of lymphoma subtypes, there were 181 (50%) aggressive B‐

NHL, of which 127 patients with DLBCL and 47 with MCL. 107 pa-

tients (30%) with indolent B‐NHL, of which 62 patients with FL, 18

MZL, 9 SLL, 7 LPL. 27 (7.5%) patients with T‐NHL and 45 (12.5%)

with HL. The median follow‐up from the diagnosis of COVID‐19 was

3 months (1‐13), 48% of patients had to be admitted to the hospital.

Out of those who required hospitalization died 40% . Overall mor-

tality rate was 21%.

There was no difference in mortality between NHL subtypes,

while patients with HL had a signiﬁcantly lower risk of mortality

(hazard ratio 0.32, 95% CI [0.158, 0.648], P 0.04). However, there

were fewer patients (44%) with HL on the active treatment of lym-

phoma, compared to the whole group of NHL (56%), in the group of

aggressive NHL even 64%. A lower median age of patients with HL

(47) may also contribute to this ﬁnding.

Active treatment of lymphoma at the time of infection repre-

sented a signiﬁcantly higher risk of death (hazard ratio 2.25, 95% CI

[1.428, 3.546], P 0.001). We did not show a statistically signiﬁcantly

higher mortality with rituximab containing regimens compared to

chemotherapy alone. A higher risk of mortality was demonstrated in

patients with relapsed, progressive disease (Hazard Ratio 2.08, 95%

CI [1.073, 4.034], P 0.01).

Our data conﬁrm an increased risk of mortality, especially in

patients with NHL, compared to the general population. The slightly

lower risk of mortality compared to previously published data can be

explained by the higher incidence of cases with a milder course,

recorded for analysis, treated only on an outpatient basis for COVID‐

19, which did not require hospitalization. The higher risk for patients

in active treatment suggests the need for active immunization before

treatment, where possible, and the need for effective therapy in case

of infection during ongoing anti‐tumor therapy, including the use of

monoclonal antibodies to treat COVID‐19 infection.

Keywords: Cancer Health Disparities

No conﬂicts of interests pertinent to the abstract.

286 |OUTCOMES OF PATIENTS WITH LYMPHOMA AND

COVID‐19: AN OBSERVATIONAL COHORT STUDY FROM

GELTAMO SPANISH GROUP

A. Martín García‐Sancho

, M. Izuzquiza

, M. Bastos‐Oreiro

, M.

Baile

, S. Nistal

, M. Cortés

, A. Jiménez‐Ubieto

, B. Rey Búa

, H.

Guillén‐García

, J. Cannata‐Ortiz

, S. Novelli

, M. I. Gómez‐Roncero

F. J. Peñalver

, E. M. González Barca

, M. Infante

, M. Jesús

Peñarrubia

, M. Franch

, C. Alonso‐Prieto

, I. Zeberio

, B. Sán-

chez‐González

, A. Muntañola

, F. Hernández‐Mohedo

, X.

Martín‐Martitegui

, J. María Arguiñano

, R. del Campo

, L.

Escoda

, A. Roldán‐Pérez

, Á. Ramírez‐Payer

, H. Luzardo

, S.

Lorente

, M. Solé‐Rodríguez

, P. Abrisqueta

, J. M. Sancho

Hospital Universitario de Salamanca and IBSAL, Hematology

Department, Salamanca, Spain,

Hospital Vall d’Hebron, Hematology

Department, Barcelona, Spain,

Hospital Gregorio Marañón, Hematology

Department, Madrid, Spain,

Hospital Universitario HLA Moncloa,

Hematology Department, Madrid, Spain,

Hospital 12 de Octubre,

Hematology Department, Madrid, Spain,

Hospital Universitario de

Guadalajara, Hematology Department, Guadalajara, Spain,

Hospital

Universitario La Princesa, Hematology Department, Madrid, Spain,

Hospital de la Santa Creu i Sant Pau, Hematology Department,

Barcelona, Spain,

Hospital Virgen de la Salud, Hematology Department,

Toledo, Spain,

Hospital Universitario Fundación Alcorcón, Hematology

Department, Alcorcón, Madrid, Spain,

Institut Català d’Oncologia,

Hospital Duran i Reynals, IDIBELL, Univertitat de Barcelona, Hematology

Department, Barcelona, Spain,

Hospital Infanta Leonor, Hematology

Department, Madrid, Spain,

Hospital Clínico Universitario de

Valladolid, Hematology Department, Valladolid, Spain,

Hospital

Germans Trias i Pujol, Hematology Department, Barcelona, Spain,

Hospital Arnau de Vilanova, Hematology Department, Valencia, Spain,

Hospital Universitario de Donostia, Hematology Department,

Donostia‐San Sebastian, Spain,

Hospital del Mar, Hematology

Department, Barcelona, Spain,

Hospital Universitario Mutua Terrassa,

Hematology Department, Terrassa, Barcelona, Spain,

Hospital Virgen

de las Nieves, Hematology Department, Granada, Spain,

Hospital

Universitario Cruces, Hematology Department, Bilbao, Spain,

Complejo

Hospitalario de Navarra, Hematology Department, Pamplona, Spain,

Hospital Son Llàtzer, Hematology Department, Palma de Mallorca,

Spain,

Institut Català d’Oncologia, Hospital Joan XXIII, Hematology

Department, Tarragona, Spain,

Hospital Infanta Sofía, San Sebastián

de los Reyes, Hematology Department, Madrid, Spain,

Hospital Central

de Asturias, Hematology Department, Oviedo, Spain,

Hospital Doctor

Negrín, Hematology Department, Las Palmas de Gran Canaria, Spain,

Hospital Vithas Xanit Internacional, Benalmádena, Hematology

Department, Málaga, Spain,

Hospital Juan Ramón Jiménez, Hematol-

ogy Department, Huelva, Spain

Introduction: COVID‐19 is thought to be more frequent and severe

in patients with cancer. Lymphoma patients may be especially

vulnerable, due to the immunodeﬁciency and immune dysregulation

caused by the lymphoma itself and the antitumor treatments. This

study describes the characteristics and outcomes of lymphoma pa-

tients after developing COVID‐19.

Methods: This is a retrospective multicentre study carried out in the

hospitals of the GELTAMO group, which included patients with a

histological diagnosis of lymphoma and conﬁrmed SARS‐COV‐2

infection before June 30

, 2020. The primary outcome was overall

survival (OS) 60 days after a COVID‐19 diagnosis.

380

SUPPLEMENT ABSTRACTS

Results: A total of 218 patients (median sage 69.5 [21‐94] years, 54%

male) were included; 100 patients had an indolent B‐cell non‐

Hodgkin's lymphoma (NHL), 67 aggressive B‐cell NHL, 19 mantle‐

cell lymphoma, 15 peripheral T‐cell lymphoma, and 17 Hodgkin's

lymphoma. Patients had received a median of 1 line (0‐7) of therapy,

and 44.9% were on active treatment at the time of COVID‐19

diagnosis. Only 6.4%, 1.8% and 0.9% of patients had received pre-

viously autologous stem‐cell transplantation, allogeneic SCT and

CAR‐T cell therapy, respectively. 89% of patients were hospitalized,

71% required oxygen, and 15% mechanical ventilation. With a me-

dian follow‐up of 91.5 days (13‐203), 65 patients have died (60 from

COVID‐19, 4 from lymphoma, 1 due to other causes), with an esti-

mated 60‐day OS of 68.6% (95% CI 62.1–75.1) (ﬁgure 1A). In uni-

variate analysis, baseline characteristics associated with decreased

OS were age ≥70 years, hypertension, diabetes, other cancer, active

disease and hypogammaglobulinemia, but only age ≥70 years main-

tained independent inﬂuence in the multivariate analysis (HR 3.29,

95% CI 1.86‐5.83, p <0.001). Active treatment did not signiﬁcantly

impact OS (ﬁgure 1B). Univariate analysis revealed different prog-

nostic factors, apart from age, for patients with DLBCL (N =60) and

FL (N =69). While the presence of active disease had a prognostic

impact on DLBCL (60‐day OS 56% vs 79%, p =0.038) but not on FL

(60‐day OS 65% vs 78%, p =0.181) patients, the opposite occurred in

the case of active treatment, which seemed to have a negative in-

ﬂuence only in patients with FL, as shown in ﬁgures 1C and 1D.

Conclusions: Our results conﬁrm a high mortality in patients with

lymphoma and COVID‐19, especially in those ≥70 years old. In

patients with DLBCL, disease control seems essential to reduce the

risk of mortality in the event of contracting the infection. By contrast,

in patients with FL, delaying the start of treatment until it is not

strictly necessary should be considered, and these patients should be

prioritized to be vaccinated before starting antitumor treatment. This

study provides initial data to develop recommendations for the

management of lymphoma patients during the COVID‐19 pandemic.

Keywords: Lymphoid Cancers – Other, Therapeutics and Clinical

Trials in Lymphoma ‐Other

No conﬂicts of interests pertinent to the abstract.

286 bis | SEROLOGICAL RESPONSES AFTER SARS‐COV‐2

VACCINATION FIRST DOSE IN PATIENTS WITH LYMPHOID

MALIGNANCY: FIRST INTERIM ANALYSIS OF THE UK PROSECO

STUDY

S. H. Lim,

1,2

N. Campbell,

D. Joseph‐Pietras,

M. Johnson,

Mundy,

H. Coleman,

T. Wynn,

B. Maynard,

R. Lown,

A. Bates,

Wetherall,

D. Muller,

J. Falconer,

C. Fox,

G. Collins,

A. O'Call-

aghan,

V. Willimott,

M. Ahearne,

S. N. Faust,

P. W. Johnson,

1,2

Goldblatt,

A. J. Davies.

1,2,4

Centre for Cancer Immunology, University of Southampton,

Southampton, UK,

Cancer Research UK Centre, University of

Southampton, UK,

University Hospital Southampton NHS Foundation

Trust, Southampton, UK,

NIHR/Cancer Research UK Southampton

FIGURE 1 Overall survival in the whole series (A), and according to active treatment in the whole series (B), in patients with diffuse large

B‐cell lymphoma (DLBCL) (C) and in patients with follicular lymphoma(FL) (D)

SUPPLEMENT ABSTRACTS

381

Experimental Medicine Cancer Centre, WISH Laboratory, University

Hospital Southampton, UK,

Great Ormond Street Institute of Child

Health, University College London, London, UK,

Nottingham University

Hospitals NHS Trust, Nottingham, UK,

Oxford University Hospitals NHS

Foundation Trust, Oxford, UK,

Portsmouth Hospitals University NHS

Trust, Portsmouth, UK,

Norfolk and Norwich University Hospitals NHS

Foundation Trust, Norwich, UK,

University Hospitals of Leicester NHS

Trust, Leicester, UK

Introduction: A population‐wide SARS‐CoV‐2 vaccination pro-

gramme commenced in the UK in December 2020. Two vaccines

have been widely deployed; BNT162b2 (Pﬁzer) and a ChAdOx1

nCoV‐19 (Astra Zeneca) both encoding the full length of the spike (S)

protein. The vaccines are administered in two doses 12 weeks apart,

as opposed to 3‐weekly in other countries. Studies in healthy in-

dividuals indicate that a single dose of the vaccine induces detectable

anti‐S IgG antibodies in most adults.

Patients with lymphoid malignancies risk more severe COVID‐19

and are also likely to be poor vaccine responders. PROSECO is a

prospective observational study to evaluate the robustness and

persistence of SARS‐CoV‐2 vaccine responses, and identify baseline

clinical parameters correlated to vaccine responses.

Methods: Patients with a conﬁrmed lymphoma diagnosis undergo

blood sampling prior to vaccination, 4 weeks after the ﬁrst dose, and

2‐4 weeks, 6 and 12 months after the second dose. IgG to SARS‐CoV‐

2 Spike, Receptor Binding Domain (RBD) and nucleocapsid protein

are tested using a qualiﬁed electrochemiluminescent assay (Meso-

Scale Discovery

) calibrated to the WHO International reference

serum (NIBSC 20/136) and compared to responses in healthy vol-

unteers. T‐cell reactivity against spike protein will be assessed by

ELISpot.

Results: This ﬁrst interim analysis reports the serological response of

44 participants with lymphoma (6 Hodgkin lymphoma, 12 diffuse

large B cell lymphoma, 16 follicular lymphoma, 2 mantle cell lym-

phoma, 2 chronic lymphocytic leukaemia, 2 marginal zone lymphoma,

4 peripheral T‐cell lymphoma), and data from 49 healthy volunteers

analysed on the same platform, 4 weeks after their ﬁrst dose of

vaccination. Post‐vaccination anti‐S IgG levels were signiﬁcantly

lower in patients with lymphoma (geometric mean 3.4 U/ml)

compared to healthy participants (geometric mean 331.3 U/ml

(Pﬁzer) and 66.5 U/ml (Astra Zeneca)). Among patients vaccinated

during systemic anti‐lymphoma therapy, only 2/26 had anti‐S IgG

>10 Units/ml, compared to 11/18 patients who have had no treat-

ment, or who completed therapy >6 months before the ﬁrst vacci-

nation dose. In the post‐treatment group, patients with curable

disease (n =5) had anti‐S IgG levels comparable to healthy partici-

pants. In contrast, the serological response in incurable indolent

lymphomas, 4/8 cases exhibiting poor responses despite never being

treated or completed treatment >3 years previously.

Conclusions: This initial analysis indicates that patients with lym-

phoma receiving treatment have a reduced serological response (14‐

fold vs untreated) to the ﬁrst dose of SARS‐CoV‐2 vaccination and

suggests a rationale for prompt administration of the second dose.

Patients with indolent lymphoma showed persistently poor serolog-

ical responses irrespective of treatment and might beneﬁt from

further vaccine boosters.

Keywords: Lymphoid Cancers – Other

Conﬂicts of interests pertinent to the abstract

S. N. Faust:

Fees to his institution for participation in advisory boards related to

vaccine, or grants for contract commercial clinical trials, were paid to

SNF's institution (with no personal payment of any kind) from

AstraZeneca/Medimmune, Sanoﬁ, Pﬁzer, Seqirus, Merck, GSK, J&J,

Merck and Valneva, outside the submitted work.

A. J. Davies:

Research support and honoraria from Astra Zeneca.

G. Collins:

Honoraria from Astra Zeneca and Pﬁzer, and research support from

Pﬁzer.

M. Ahearne:

Research support from Pﬁzer.

287 |EFFICACY AND SAFETY OF DARATUMUMAB FOR THE

TREATMENT OF MULTIPLE MYELOMA: A SERIES OF COCHRANE

REVIEWS

C. Hirsch

, V. Piechotta

, P. Langer

, C. Scheid

, L. John

, N. Skoetz

Cochrane Haematology, Department I of Internal Medicine, Center for

Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of

Medicine and University Hospital, University of Cologne, Cologne, Germany,

Department I of Internal Medicine, Center for Integrated Oncology Aachen

Bonn Cologne Duesseldorf, Stem Cell Transplantation Program, Faculty of

Medicine and University Hospital, University of Cologne, Cologne, Germany,

Department of Hematology, Oncology and Rheumatology, University

Hospital Heidelberg, Heidelberg, Germany,

Cochrane Cancer, Department

I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne

382

SUPPLEMENT ABSTRACTS

Duesseldorf, Faculty of Medicine and University Hospital, University of

Cologne, Cologne, Germany

Introduction: Daratumumab has approved indications for the treat-

ment of patients with newly diagnosed multiple myeloma (NDMM)

both eligible and ineligible for transplant and treatment of relapsed

or refractory multiple myeloma (RRMM). The aim was to evaluate the

efﬁcacy and safety of daratumumab for transplant‐ineligible NDMM

patients (PICO 1), transplant eligible NDMM patients (PICO 2) and

for RRMM patients (PICO 3).

Methods: For each PICO we conduct one Cochrane review according

to the standard methodology as outlined in the Cochrane Handbook

for Systematic Reviews of Interventions, and assess the certainty in

the evidence using the Grading of Recommendations Assessment,

Development and Evaluation (GRADE) approach. Our prioritised

outcomes were overall survival, adverse events (CTCAE grade ≥3)

and quality of life.

Results: Transplant‐ineligible NDMM: We identiﬁed two RCTs

(MAIA, ALCYONE) reporting on 1443 patients. Treatment with

daratumumab probably increases overall survival (HR 0.67, 95% CI

0.5 to 0.85, I

39%, moderate‐certainty evidence), results in a slight

increase of adverse events (grade ≥3) (RR 1.05, 95% CI 1.0 to 1.11, I

26%, high‐certainty evidence), more people probably gain at least 10

points of global health status after start of treatment when compared

to people receiving no daratumumab (RR 1.13, 95% CI 1.13 to 1.23, I

0%, moderate‐certainty evidence).

Transplant‐ineligible NDMM: We identiﬁed two RCTs (CASSIO-

PEIA, GRIFFIN) reporting on 1292 patients. GRIFFIN included 207

patients, but did not report any of our crucial outcomes. Treat-

ment with daratumumab may increase overall survival (HR 0.52,

95% CI 0.33 to 0.82, low‐certainty evidence), results in a

slight increase of adverse events (grade ≥3) (RR 1.06, 95% CI 1.0

to 1.13, high‐certainty evidence), more people may gain at least

10 points of global health status after start of treatment compared

to people receiving no daratumumab (RR 1.07, 95% CI 0.91 to

1.24, low‐certainty evidence) at 9.0 months after start of

treatment.

RRMM: We identiﬁed four RCTs (CANDOR, CASTOR, LEPUS,

POLLUX) reporting on 1717 patients. Treatment with dar-

atumumab probably increases overall survival (HR 0.62, 95% CI

0.49 to 0.79, I

7%, moderate‐certainty evidence). We were able to

include safety data from two trials (CASTOR, POLLUX) for 1044

patients. Treatment with daratumumab probably results in a slight

increase of adverse events (grade ≥3) (RR 1.17, 95% CI 1.04 to

1.31, I

64%, moderate‐certainty evidence) and more people may

gain at least 10 points of global health status after start of treat-

ment compared to people receiving no daratumumab (RR 1.07, 95%

CI 1.07 to 1.22, I

0%, low‐certainty evidence) at 9 months after

start of treatment.

Conclusions: Treatment with daratumumab is likely to retrieve gain

in survival, increases the risk of adverse events (grade ≥3) and may

contribute to a clinically important improvement of quality of life.

EA – previously submitted to EHA 2021.

Keywords: Multiple Myeloma

No conﬂicts of interests pertinent to the abstract.

SUPPLEMENT ABSTRACTS

383

DOI: 10.1002/hon.2881

SUPPLEMENT ABSTRACTS

PUBLICATION

LYMPHOMA BIOLOGY

288 |CCL2‐CCR2 AXIS SIGNALING PROMOTES DIFFUSE

LARGE B‐CELL LYMPHOMA CELL SURVIVAL AND INVASION

L. Yan‐Li

Anhui Medical University the First Afﬁliated Hospital of Anhui Medical

University, Pathology, Hefei, Anhui, China

Objective: Diffuse large B cell lymphoma (DLBCL) incidence rates

have increased year by year, a part of them have poor clinical

outcomes, but the underlying mechanism involved is still unclear.

Chemokines have been thought to play an important role in

occurrence and development of tumors, but they are poorly studied

in DLBCL. CC‐Chemokine Ligand 2 (CCL2), the most representative

of the CC chemokine family members, through binding to its high

afﬁnity receptor, CC chemokine receptor 2 (CCR2), has be regarded

to involve in tumor growth, angiogenesis, epithelial mesenchymal

transition, metastasis and immune escape etc. in recent years, but

the role and mechanism in DLBCL has not been reported yet. Our

preliminary study showed high expression of CCL2 or CCR2 was

correlated with clinicopathological characteristics, and an adverse

prognostic factor for overall survival (OS) and progression‐free

survival (PFS) of DLBCL patients. The purpose of this study is to

investigate the role of CCL2‐CCR2 axis signaling in DLBCL by in

vitro experiment.

Methods: CCL2 and CCR2 expression were analyzed in human

DLBCL cell lines and normal B lymphocytes by Western blot (WB)

and qPCR. CCL2 and CCR2 genes were silenced by lentivirus infec-

tion. The proliferation, migration, apoptosis and signaling pathway

were detected by CCK8, transwell, ﬂow cytometry (FC) and WB,

respectively.

Results: CCL2 and CCR2 were expressed in all human DLBCL cell

lines (SUDHL‐2, SUDHL‐4, SUDHL‐6, OCI‐Ly8 and OCI‐Ly10).

Blockade of CCL2‐CCR2 axis signaling with lentivirus infection, CCL2

neutralizing antibody or CCR2 antagonist inhibited tumor cell pro-

liferation, migration and anti‐apoptosis ability. The CCL2‐CCR2 axis

involved in the proliferation and migration of DLBCL cells by acti-

vating PI3K/Akt signaling pathway, and induced apoptosis through

activation of P38MARK signaling pathway.

Conclusions: Our study demonstrates that CCL2/CCR2 axis signaling

plays an important role in the development of DLBCL by stimulating

cell proliferation, migration and anti‐apoptosis. The inhibition of

CCL2 or CCR2 may, therefore, be a potential target for anticancer

therapy in DLBCL.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

289 |ACETYL‐COA ACETYLTRANSFERASE 1 ACTS AS A

TUMOR SUPPRESSOR IN MALIGNANT TUMORS

X. Hu

, Y. Zhang

, Y. Han

, X. Zhang

, Z. Tian

, X. Wang

Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong

University, Department of Hematology, Jinan, China,

Shandong

Provincial Hospital Afﬁliated to Shandong University, Shandong First

Medical University, Department of Hematology, Jinan, China

Background: Acetyl‐CoA acetyltransferase 1 (ACAT1) is an enzyme

to catalyze reversible formation of acetoacetyl‐CoA. Yet, the roles of

ACAT1 in malignant progression have been incompletely understood

so far. Hence, the aim of this study was to investigate the function

and signiﬁcance of ACAT1 in tumors.

Methods: In the present study, clinically annotated tumor patients

from multiple cohorts were enrolled with informed consents. Gene

expression analysis is completed through the TIMER2 web and

GEPIA2 web, based on the combination of the HPA, GTEx, and

FANTOM5 datasets. The data of protein expression is acquired from

the CPTAC dataset. The statistical signiﬁcance of survival prognosis

is analyzed by log‐rank test through the GEPIA2 web. Genetic

alteration analysis is accomplished by cBioPortal web.

Results: Aberrantly alleviated expression of ACAT1 was detected in

multiple tumors at mRNA level compared with normal cells

(Figure 1A). After including the normal tissue of the GTEx dataset as

controls, we further evaluated the expression difference of ACAT1.

ACAT1 expression levels were signiﬁcantly downregulated (tumor

versus normal) in tumor cases (Figure 1B). Similarly, the outcome of

decreased protein level of ACAT1 (tumor versus normal) could be

obtained (Figure 1C). We divided the cancer cases into high‐

expression and low‐expression groups according to the expression

levels of ACAT1 and investigated the correlation of ACAT1

expression with the prognosis of patients with different tumors.

Kaplan‐Meier curves showed stratiﬁed ACAT1

low

group were

observed with signiﬁcantly shorter overall survival (OS) and disease‐

free survival (DFS) versus the ACAT1

high

group in mutiple malignant

384

Hematological Oncology. 2021;39(S2):384–484. wileyonlinelibrary.com/journal/hon

tumors (Figure 1D and 1E). In hematological cancer, ACAT1

high

group showed a better overall survival than ACAT1

low

group in

multiple myeloma and B‐cell lymphoma (Figure 1F). Then, We

observed the genetic alteration status of ACAT1 in different tumor

samples of the TCGA cohorts. As shown in Figure 1G, the highest

alteration frequency of ACAT1 (>7%) appears for patients with

uterine tumors. The “deletion” type of copy number alteration (CNA)

was the primary type in melanoma and cervical carcinoma cases,

which show an alteration frequency of 2∼3% (Figure 1G). The

types, sites, and case number of the ACAT1 genetic alteration

SUPPLEMENT ABSTRACTS

385

are further presented in Figure 1H. We found that missense muta-

tion of ACAT1 was the main type of genetic alteration (N=48)

(Figure 1H). Additionally, we explored the potential association be-

tween genetic alteration of ACAT1 and the clinical survival prognosis

of cases with different types of cancer. The data of Figure 1I indi-

cated a better overall survival in cases without altered ACAT1

compared with cases with ACAT1 alteration in variety of

malignancies.

Conclusion: Taken together, the present study was the ﬁrst pan‐

cancer analysis on the role of ACAT1 in tumors. ACAT1 was down‐

regulated and conferred independent prognostic signiﬁcance, high-

lighting the effectiveness and potential of ACAT1 as a potential

target for future therapeutic strategies.

EA – previously submitted to EHA 2021.

The research was funded by: This study was funded by National Nat-

ural Science Foundation (No.82000195, No.82070203, No.81770210,

No.81473486 and No.81270598); Key Research and Development

Program of Shandong Province (No.2018CXGC1213); Technology

Development Projects of Shandong Province (No.2017GSF18189);

Translational Research Grant of NCRCH (No.2021WWB02,

No.2020ZKMB01); Shandong Provincial Natural Science Foundation

(No.ZR2020QH094); Taishan Scholars Program of Shandong Province;

Shandong Provincial Engineering Research Center of Lymphoma; Ac-

ademic Promotion Programme of Shandong First Medical University

(No. 2019QL018; No.2020RC007); Technology Development Project

of Jinan City (No.200027182); Shandong Provincial Hospital Youth

Talent Plan; Shandong Provincial Hospital Research Incubation Fund.

Keywords: Bioinformatics, Computational and Systems Biology,

Diagnostic and Prognostic Biomarkers

No conﬂicts of interests pertinent to the abstract.

290 |CONCURRENT COMPOSITE LYMPHOMAS

COLLECTIVELY BEARING THREE DIAGNOSTIC ENTITIES OF

SHARED CLONAL ORIGIN

W. Alduaij

, M. Al Moosawi

, H. Leitch

, J. Craig

BC Cancer, Lymphoid Cancer Research, Vancouver, Canada,

University of British Columbia, Hematological Pathology, Department of

Pathology and Laboratory Medicine, Vancouver, Canada,

University of

British Columbia, Hematology, Vancouver, Canada,

BC Cancer,

Department of Pathology and Laboratory Medicine, Vancouver, Canada

Introduction: Composite lymphoma (CL) is deﬁned as the coexistence

of two distinct lymphoma subtypes in a single biopsy, whereas

discordant lymphoma (DL) is their occurrence at different anatomical

sites. Although CL/DL with two distinct lymphomas are a well‐

described phenomenon, the diagnosis of three lymphomas simulta-

neously is a much rarer occurrence, with only a few cases reported in

the literature. We report a unique case involving two composite

lymphomas collectively bearing three distinct diagnostic entities:

diffuse large B‐cell lymphoma (DLBCL), classic Hodgkin lymphoma

(cHL) and follicular lymphoma (FL).

Case report: A 48‐year‐old man presented with cervical lymph-

adenopathy and a tongue mass. Cervical lymph node biopsy

revealed a composite tumour consisting of cHL and DLBCL with a

germinal centre B‐cell (GCB) phenotype by Hans algorithm. In

contrast, the tongue mass biopsy revealed a composite tumour of a

morphologically and immunophenotypically similar DLBCL, with FL

grade 3B as evidenced by uniform atypical centroblastic cells

exhibiting a nodular growth pattern suggestive of neoplastic follicle

formation conﬁrmed by intact CD21‐positive follicular dendritic

cell meshwork. Images highlighting the distinct morphological and

immunohistochemical features of all tumour components will

be presented. The DLBCL components showed no evidence of

MYC rearrangement using break‐apart ﬂuorescence in situ hybrid-

ization probes. In situ hybridization for Epstein Barr virus RNA was

positive in the Hodgkin cells in the cHL component but negative in

the other tumours. Although multiplex polymerase chain reaction

analysis using BIOMED‐2 primers failed to identify clonal rear-

rangements in IGH, the same clonal IGK rearrangement was

detected in all four tumour components, consistent with a shared

B‐cell clonal origin. The Vk‐Kde/intron‐Kde reaction identiﬁed a

single prominent peak at 377 base pair (bp) length ampliﬁed by the

Vk2f/Vk4/Vk5‐Kde primer set, consistent with a clonal B‐cell

population (Vk‐Kde 3, Fig. 1A‐C). The same peak was identiﬁed

in all four tumour components, including the nodal cHL, albeit at a

lower amplitude in keeping with the lower tumour cell content

of cHL (Fig. 1D). The patient sustained a complete remission

following rituximab, cyclophosphamide, doxorubicin, vincristine and

prednisone.

Conclusion: This case represents an exceedingly rare example of

simultaneous composite lymphomas and the concurrent diagnosis of

three histologically distinct lymphoma subtypes. It also highlights the

limitations of IGH‐based clonality testing in germinal centre B‐cell‐

derived lymphomas and underscores the importance of adequate

tissue sampling to facilitate deﬁnitive diagnosis. Given the paucity of

data on optimal therapy for these heterogeneous lymphomas, the

treatment approach should be individualized, considering all disease

components.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Pathology and

Classiﬁcation of Lymphomas

No conﬂicts of interests pertinent to the abstract.

386

SUPPLEMENT ABSTRACTS

291 |COMPREHENSIVE TRANSCRIPTOME ANALYSIS

IDENTIFIES DISTINCT COMPETING ENDOGENOUS RNA

NETWORK IN CHRONIC LYMPHOCYTIC LEUKEMIA

Y. Zhang

, X. Zhang

, Y. Han

, Z. Tian

, X. Hu

, X. Wang

Shandong Provincial Hospital Afﬁliated to Shandong First Medical

University, Department of Hematology, Jinan, China

Introduction: Increasing studies have identiﬁed that non‐coding

RNAs play critical roles in the initiation and progression of tumors

via participating in competitive endogenous RNA (ceRNA) networks.

However, the roles and functions of the ceRNA network in chronic

lymphocytic leukemia (CLL) remain poorly understood. This study

aims to explore the molecular mechanism of CLL and provide po-

tential prognostic markers and therapeutic targets through the in-

tegrated analysis of the ceRNA network in CLL.

Methods: The expression proﬁle of RNAS of CLL patients, CLL cell

lines (MEC‐1 and EHEB) and healthy group were obtained by the

illumina sequencing. R software was used for functional enrichment

analysis. The data in the genome microarray map GSE22762 was

used for survival analysis. The lncRNA/circRNA‐miRNA‐mRNA

ceRNA networks were visualized by Cytoscape 3.7.2. Four DEmRNAs

and the circRNA hsa_circ_0007675/hsa‐miR‐185‐3p/TCF7L1 axis

were veriﬁed by Quantitative real‐time PCR.

FIGURE 1

SUPPLEMENT ABSTRACTS

387

Results: In the present study, 57 differentially expressed‐(DE‐)

mRNAs, 1391 DElncRNAs, 335 DEmiRNAs and 10013 DEcircRNAs

were identiﬁed comparing CLL patients with healthy donors.

Meanwhile, 482 mRNAs, 6085 lncRNAs, 302 miRNAs and 1847

circRNAs were explored differently expressed between CLL cell

lines and healthy donors. GO and KEGG analysis results showed

that these differentially expressed genes (DEGs) are related to the

occurrence and development of tumors. The survival analyses

showed that 16 DEGs (INIP, IL3RA, CHD1, NLRP12, IL20RB,

B3GALT4, SIT1, ACOT8, AGFGR, PCLAF, C19orf18, SELENOS,

FIGURE 1

388

SUPPLEMENT ABSTRACTS

OR7A17, PCDH7, HNRNPC, PHGDH) were signiﬁcantly differen-

tially expressed.

The ceRNA network were constructed by Cytoscape software. In

total, 11 mRNA nodes, 19 miRNA nodes, 105 lncRNA nodes were

identiﬁed as differentially expressed proﬁles between CLL patients

and control. Meanwhile, a total of 256 DEcircRNAs, 19 DEmiRNAs,

and 11 DEmRNAs were employed to construct the ceRNA network

between CLL patients and control. We veriﬁed four DEGs (TCF7L1,

TRIM34, SLC30A10, HOXD4) and the circRNA hsa_circ_0007675/

hsa‐miR‐185‐3p/TCF7L1 axis. Compared with normal people, the

expression of these four genes and hsa_circ_0007675 in patient

specimens were signiﬁcantly increased whereas the expression of

hsa‐miR‐185‐3p was downregulated (p <0.05).

Conclusion: In this study, we identiﬁed the expression proﬁle of

RNAs in CLL patients and CLL cell lines. Functional enrichment

analysis and survival analysis revealed the potential functions of

DEGs. The ceRNA network we established can help to further un-

derstand the pathogenesis of CLL and provide potential prognostic

markers and novel therapeutic targets.

The research was funded by: This study was funded by National Natural

Science Foundation (No.82000195, No.82070203, No.81770210,

No.81473486 and No.81270598); Key Research and Development

Program of Shandong Province (No.2018CXGC1213); Technology

Development Projects of Shandong Province (No.2017GSF18189);

Translational Research Grant of NCRCH (No.2021WWB02,

No.2020ZKMB01); Shandong Provincial Natural Science Foundation

(No.ZR2020QH094); Taishan Scholars Program of Shandong Province;

Shandong Provincial Engineering Research Center of Lymphoma; Ac-

ademic Promotion Programme of Shandong First Medical University

(No. 2019QL018, No.2020RC007); Technology Development Project

of Jinan City (No.200027182); Shandong Provincial Hospital Youth

Talent Plan; Shandong Provincial Hospital Research Incubation Fund.

Keywords: Diagnostic and Prognostic Biomarkers, Chronic

Lymphocytic Leukemia (CLL)

No conﬂicts of interests pertinent to the abstract.

292 |THE ROLE OF MULTIPARAMETRIC FLOW CYTOMETRY

IN DETECTING AND CHARACTERIZING GAMMA‐DELTA T‐CELL

ENTITIES IN PERIPHERAL BLOOD. SINGLE‐CENTER CASE SERIES

AND LITERATURE REVIEW

F. Martín Moro

, I. Martín Rubio

, R. Alonso

, C. López

, J. Marquet

F. Herrera

, I. Delgado Trillo

, P. Herrera

, J. A. García Vela

Hospital Universitario Ramón y Cajal, Hematology Department, Madrid,

Spain,

Hospital Universitario de Getafe, Hematology Department,

Madrid, Spain

Introduction:Gamma‐delta (GD) T‐cell lymphoid neoplasms are rare

and frequently aggressive tumours whose detection and character-

ization by ﬂow cytometry (FCM) is challenging in a huge proportion

of cases, specially those with leukemic involvement. Sometimes it is

difﬁcult to distinguish between clonal/malignant and normal/poly-

clonal populations. Our aim is to present a case series of GD T‐cell

entities – focalizing in FCM ﬁndings – and review the role of FCM

according to the current literature.

Methods: Four different and illustrative cases of GD T‐cell expansion

in peripheral blood (>5% of all lymphocytes) occurred in a single‐

center were reviewed. FCM methodology: eight‐colour instrument

(FACSCanto

II) with previous compensation and calibration,

EuroFlow panels (screening LST and complete diagnosis T‐CLPD.

ALOT and T‐ALL if necessary), LoQ 0.01%, Inﬁnicyt

Software 2.0.

Normal and clonal/pathological GD T‐cells populations were

described. Clonally TCR‐gamma gene rearrangements detection was

performed by multiplex PCR (BIOMED‐2). A literature review was

performed to describe the characteristics of the most relevant GD

T‐cell entities.

Results: Case 1 was diagnosed with hepatosplenic T‐cell lymphoma

(HSTL), case 2 with GD T‐cell large granular lymphocytic leukemia

(GD T‐LGL), case 3 with GD T‐ALL (T‐cell acute lymphoblastic leu-

kemia/lymphoma), and case 4 with polyclonal GD T‐cell expansion

secondary to infectious mononucleosis caused by EBV. Characteris-

tics for each case – including the most relevant immunophenotypic

ﬁndings by FCM – are summarized in Figure 1. Two other GD T‐cell

lymphomas were included in the review although their peripheral

blood involvement is scarcely reported: primary cutaneous GD T‐cell

lymphoma (PCGD‐TCL) and monomorphic epitheliotropic intestinal

T‐cell lymphoma (MEITL).

Conclusions: The peripheral blood assessment by FCM is able to

distinguish and characterize leukemic GD T‐cell entities if the

methodology is correctly performed. The loss of expression of T‐

cell markers such as CD5 or CD7 is a common ﬁnding in GD T‐

cell neoplasms. Most cases are CD4 negative with a negative to

positive expression of CD8. Although a cytotoxic pattern is com-

mon – except for GD T‐ALL – there is variability in markers

expression, i.e. CD57, CD16, and Granzyme B. Analysing the T‐cell

subset and the expression of other markers such as CD94, TdT,

and CD103v may also be helpful. It is mandatory to integrate FCM

with clinical, morphological, and genetic ﬁndings to diagnose ma-

lignant and reactive GD T‐cell entities with peripheral blood

involvement.

Keywords: Diagnostic and Prognostic Biomarkers, Imaging and Early

Detection – Other, Lymphoid Cancers ‐Other

No conﬂicts of interests pertinent to the abstract.

SUPPLEMENT ABSTRACTS

389

390

SUPPLEMENT ABSTRACTS

293 |TRACKING THE EVOLUTION OF UNTREATED HIGH‐

INTERMEDIATE/HIGH‐RISK DIFFUSE LARGE B‐CELL LYMPHOMA

BY CIRCULATING TUMOR DNA

S. Zhang

, T. Zhang

, Z. Song

, W. Li

, J. Yu

, J. Zhao

, S. Zhou

Z. Qian

, L. Li

, L. Qiu

, X. Liu

, X. Wang

, H. Zhang

Department of Lymphoma, Tianjin Medical University Cancer Institute

and Hospital, National Clinical Research Center of Cancer, Key Laboratory

of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for

Cancer, the Sino‐US Center for Lymphoma and Leukemia Research,

Tianjin, China

Background: Diffuse large B‐cell lymphoma (DLBCL) is aggressive and

easy to relapse, and the potential to noninvasively monitor tumor

evolutionary dynamics of DLBCL needs to be further established.

Liquid biopsy has been proved a promising method to access tumor

DNA through blood sample. In the current study the feasibility and

clinical signiﬁcance of circulating tumor DNA (ctDNA) for DLBCL were

assessed.

Methods: A total of 19 tumor biopsy samples and 38 plasma samples

from 40 de novo high‐intermediate/high‐risk DLBCL patients were

evaluated at baseline. Longitudinal blood samples collected under

chemotherapy were also collected. A targeted sequencing gene panel

including 31 genes that are most frequently mutated in lymphoma was

designed for this study. The gene mutation spectrum of DLBCL was

analyzed via a recently developed methodology termed Circulating

Single‐Molecule Ampliﬁcation and Resequencing Technology

(cSMART).

Results: The median age of the patients was 59 years.Variants were

identiﬁed in 32 (84%) patients. The mutation of genes detected with

10% or higher ratios include TP53 (42.1%), KMT2D (28.9%), CARD11

(21.1%), CREBBP (15.8%), B2M (15.8%), TNFAIP3 (15.8%), CD79B

(13.2%), EP300 (13.2%), myc (10.5%), TRAF3(10.5%). Compared with

the tumor tissue, ctDNA proﬁling showed good concordance (67.1%).

More mutation sites could be detected in ctDNA than those in matched

tumor tissue. ctDNA concentration at baseline was correlated with

tumor burden, LDH and IPI score. In addition, patients with mutated

TP53 and B2M before treatment predicted poor prognosis. Serial

ctDNA analysis showed that the concentration of ctDNA has utility for

real‐time assessment of treatment response and increase of ctDNA

level could predict progressive disease or clinical recurrence.

Conclusion: Our results demonstrate that ctDNA analysis is a

promising method for detection of mutation spectrum of DLBCL and

disease surveillance during therapy.

EA – previously submitted to regional or national meetings (up to

1000 attendees).

The research was funded by: The research was funded by the

Natural Science Foundation of Tianjin (19JCYBJC26500) and the

Clinical Oncology Research Fund of CSCO (Y‐XD2019‐162).

Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B‐cell

non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

294 |T‐CELL SUBSET COMPOSITION AND FUNCTIONALITY IN

PATIENTS WITH WALDENSTRÖM'S MACROGLOBULINEMIA

K. Amaador

, A. W. J. Martens

, R. de Boer

, J. M. Rietveld

E. Eldering

, M. J. Kersten

, A. P. Kater

, J. M. I. Vos

, S. H. Tonino

Amsterdam UMC, University of Amsterdam, Department of Hematology,

Cancer Center Amsterdam, Amsterdam, The Netherlands and Lymphoma

and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, Netherlands,

Amsterdam Infection & Immunity Institute, Department of Experimental

Immunology, Amsterdam UMC, Amsterdam, The Netherlands,

Amsterdam, Netherlands

Background: Waldenström's macroglobulinemia (WM) is an incur-

able low‐grade B‐cell Non‐Hodgkin lymphoma. WM resembles

chronic lymphocytic leukemia (CLL) with regard to biologic and

clinical characteristics. In CLL, extensive abnormalities in T‐cell

subset distribution and function have been described. These alter-

ations may contribute to disappointing responses to T‐cell directed

immunotherapies. Novel autologous T‐cell directed immunotherapy

may improve the outlook for WM patients. However, studies evalu-

ating T‐cell functionality in WM are lacking.

Methods: We systematically evaluated peripheral blood (PB) T‐cell

subset composition and function in WM patients. PB samples

were collected from treatment‐naive, relapsed and symptomatic

WM patients, HCs and treatment‐naïve CLL patients. Lymphocyte

phenotyping was performed and differences in functionality

were assessed by determining the potential of T‐cells to degranu-

late and produce cytokines. Cytotoxic potential was assessed

via engagement of blinatumomab (CD3 x CD19 bi‐speciﬁc T‐cell

engager), that re‐directs T‐cells via CD3 to kill CD19

tumor

cells. Correlations between T‐cell subset numbers, cytokine

production, cytotoxic capacity and markers of disease activity

were performed for treatment‐naïve and pretreated WM

separately.

Results: This study included 16 treatment‐naïve WM patients, 10

pretreated symptomatic WM patients, 21 age‐matched HCs and 17

treatment‐naïve CLL patients. In WM patients, following cell types

had counts similar to HCs: T‐cells (relative), CD4

T‐cells (relative),

absolute CD4

and CD8

T‐cells, T

cells, T

reg

cells, and Vδ1/ Vδ2 T‐

cells (relative). This is in contrast to CLL, in which T‐cell numbers

(relative) were decreased, absolute CD4

and CD8

T‐cells were

increased compared to HCs, T

, T

reg

, and Vδ1 T‐cell numbers were

increased as expected. CD4

/CD8

T‐cell differentiation was normal

in WM as opposed to CLL in which a known skewing towards ter-

minal differentiation in CD8

T‐cells was observed. No difference in

Vδ2 T‐cell count was observed between all groups (Figure 1). No

signiﬁcant differences were found in cytokine production and

degranulation between CD4

and CD8

T‐cells from WM patients in

comparison with HCs, in contrast to CLL in which decreased amounts

of TNF‐α and increased expression of CD107a were found. Cytotoxic

potential of WM‐derived T‐cells was intact and similar to HCs, while

CLL‐derived T‐cells have impaired cytotoxic response to

blinatumomab.

SUPPLEMENT ABSTRACTS

391

Conclusion: These data represent the ﬁrst systematic evaluation of

the T‐cell compartment in WM. The qualitative and quantitative

changes in the immune system seen in CLL are not found in WM; T‐

cell numbers, distribution and functionality seem mostly preserved

even in pretreated patients. These ﬁndings are encouraging for

application of T‐cell directed immunotherapy in WM, especially for

relapsed/refractory WM.

Keywords: Immunotherapy, Indolent non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

295 |INFLUENCE OF EPSTEIN BARR VIRUS (EBV) EXPRESSION

ON CD4+T CELLS AT THE MICROENVIRONMENT IN PEDIATRIC

HODGKIN LYMPHOMA

O. Jimenez

, M. V. Preciado

, E. De Matteo

, P. Chabay

Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas

(IMIPP). CONICET‐GCBA, Hospital de Niños Ricardo Gutiérrez. División

Patología, Buenos Aires, Argentina

Introduction: A unique feature of Hodgkin lymphoma (HL) is the

presence of CD4+T cells that surround, protect, and promote

survival of tumor cells. It was described that primary EBV infection

elicits EBV‐speciﬁc CD4+T cells with cytotoxic proteins. Since in

Argentina, a high incidence of EBV‐associated lymphoma was

described in pediatric cases, our aim was to evaluate EBV inﬂu-

ence on CD4+T cells at the microenvironment in pediatric

patients.

Methods: 42 pediatric patients with HL were included in this study.

EBV presence was evaluated by EBERs in situ hybridization (ISH) and

LMP1 immunohistochemistry (IHC). CD4, CD8, Foxp3, Tbet, GrB,

IL10, PD1 and CD56 markers were analyzed by IHC. Survival was

evaluated by Kaplan Meier analysis.

Results: EBV expression in HRS tumor cells was observed in 78% of

patients by EBERs ISH and LMP1 IHC. Mean CD4+cell count was

not statistically different between EBV+and EBV‐patients (p >0.05,

MW test). However, when functional markers of CD4+cells were

evaluated, exclusively in EBV+cases, CD4+cells positively corre-

lated with GrB+cells (p =0.008, r =0.473, Spearman), whereas

neither Foxp3+nor Tbet+cells showed statistical correlation with

CD4+cells (p >0.05, Spearman). CD4+cells also displayed a sta-

tistical positive correlation with CD56+cells, as marker of NK cells

(p =0.006, r =0.488, Spearman), while, in contrast, in EBV‐cases a

trend to a negative correlation was demonstrated between CD4+

and CD56+cells (p =0.06, r =‐0.686, Spearman). Furthermore,

CD56+cells did not show a statistical correlation with GrB+cells

(p >0.05, Spearman). In addition, Tbet+cells correlated with Foxp3+

and GrB+cells (p =0.001, r =0.536; p =0.04, r =0.364, respec-

tively) in EBV+cases whereas Foxp3+cells correlated with GrB+

cells (p =0.013, r =0.444, Spearman). All those correlations were not

observed in EBV‐cases. None of the markers were associated with

event free survival when median cells count was used as cut off value

(p >0.05, long rank test).

Conclusions: This study reﬂects that CD4 cells in the context of EBV‐

associated pediatric HL may be involved in cytotoxic activity as

observed in primary infection, and this activity could be direct, since

NK cells were not correlated with cytotoxic GrB marker. In addition,

this cytotoxic and proinﬂammatory activity of GrB+and Tbet+cells,

respectively, may be counterbalanced by immunoregulatory Foxp3+

cells.

Keywords: Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

296 |COSTIMULATORY MOLECULE OX40, TUMOR IMMUNE

MICROENVIRONMENT AND RESPONSE TO

IMMUNOCHEMOTHERAPY IN DIFFUSE LARGE B‐CELL

LYMPHOMA: AN INTEGRATIVE ANALYSIS WITH MOLECULAR

CHARACTERISTICS

X. Wang

, Y. Hong

, Y. Li

, Q. Guan

, S. Zhou

, Z. Qian

, L. Qiu

, L. Li

X. Liu

, K. Fu

, H. Zhang

Department of Lymphoma, Tianjin Medical University Cancer Institute

and Hospital, National Clinical Research Center of Cancer, Key Laboratory

of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for

Cancer, the Sino‐US Center for Lymphoma and Leukemia Research,

Tianjin, China

Background: OX40 is a crucial T‐cell costimulatory molecule, but its

molecular characteristics remain unclear in diffuse large B‐cell lym-

phoma (DLBCL).

Methods: We performed an integrative analysis of gene expression,

somatic mutations and multiplex immunoﬂuorescence to charac-

terize the OX40 molecular features, tumor immune microenviron-

ment (TiME) and clinical outcomes.

Results: We ﬁrst identiﬁed that an abnormally higher gene

expression of OX40 existed in DLBCL than other cancers from

discovery cohort, which was validated in two independent cohorts.

Then, we found that elevated OX40 promoted DLBCL patients to

have superior response to immunochemotherapy via activating T‐

cell from another discovery cohort and validation cohort. Elevated

OX40 drove the recruitment of abundant inﬁltrating lymphocytes,

leading a higher stromal‐immune score in TiME, and positively

corrected with immune‐related genes, including PD‐1, CTLA4,

TIGIT, VISTA, ICOS, GITR, 4‐1BB and CD28. Tumor mutational

burden was not a mainly driver of host immune responses mediated

by elevated OX40, but BIRC6, STAT6 and TNFRSF14 mutations. In

another validation cohort, patients with high OX40 expression

exhibited lower Ann Arbor stage (p =0.039) and IPI score

(p =0.047), and were easier to achieve CR/PR, especially in both

high OX40 and OX40L expression, and have longer OS (p =0.008)

and PFS (p =0.010). In inﬁltrated T‐cell subsets analysis, patients

392

SUPPLEMENT ABSTRACTS

with a greater number of CD4+/OX40+or CD8+/OX40+T‐cells

had a longer OS (p =0.021; p =0.009), while the CD8+/OX40+

T‐cells also maintained independent prognostic value for survival

(HR =0.517; CI =0.276‐0.968; p =0.039).

Conclusions: Overall, our ﬁndings provide insights for the application

of targeting OX40, or a combined OX40 agonists and ﬁrst‐line

immunochemotherapy in DLBCL patients.

The research was funded by: The research was funded by

Natural Science Foundation of Tianjin grants (19JCYBJC26500),

Clinical Oncology Research Fund of CSCO grants (Y‐XD2019‐162,

Y‐Roche20192‐0097).

Keywords: Basic and Translational Science ‐Other, Aggressive B‐cell

non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

297 |A WIDE T‐CELL EXHAUSTION PATTERN IS FREQUENTIN

THE TUMOR MICROENVIRONMENT OF RELAPSED/

REFRACTORY B‐CELL LYMPHOMA PATIENTS AND COULD BE

CIRCUMVENTED BY PDL1 BLOCKADE

C. Laurent

, C. Syrykh

, C. Herbaux

, E. Gat

, P. Gravelle

, K. Tarte

G. Cartron

, L. Xerri

IUCT‐Oncopole Toulouse CRCT INSERM U1037, Pathology, Toulouse,

France,

CHU Montepellier UMR CNRS 5235, Hematology, Montpellier,

France,

LYSARC CHU Lyon Sud, LYSARC, Pierre‐Bénite, France,

CHU

Rennes Pontchaillou UMR U1236, Immunology, Cell Therapy and He-

matopoiesis, Rennes, France,

Institut Paoli‐Calmettes, Centre de

Recherche en Cancérologie de Marseille, INSERM U1068, CNRS

UMR7258, Pathology, Marseille, France

Background: Relapsed/refractory (R/R) B‐cell non‐Hodgkin lym-

phomas (B‐NHL) remain incurable diseases and need novel thera-

peutic approaches. In the LYSA trial GATA (NCT03276468), 58

DLBCL and 58 FL R/R patients were treated by obinutuzumab (OBI)

combined with BCL‐2 inhibitor venetoclax (VEN) and anti‐PDL1

atezolizumab (ATE) in order to test the synergy of chemo‐free

tumor‐targeted therapies. The goal of the present study was to

evaluate the inﬂuence of tumor microenvironment (TME) on the ef-

ﬁciency of this novel drug combination.

Methods: A centralized pathological review was mandatory for

all enrolled cases. As a result, 67 cases including 35 DLBCL

(16 GC and 19 non‐GC subtypes) and 32 FL (grade 1‐2) with suf-

ﬁcient relapse material were selected for evaluating TME compo-

sition and immune checkpoints (ICP) expression using standard and/

or multiplexed IHC analyses. All stainings have been scored manu-

ally, and when possible validated using a computer‐assisted soft-

ware. Biopsy samples at diagnosis were also analyzed in 60%

of cases. Non‐parametric tests were used to test correlations be-

tween TME parameters and clinical responses assessed by Lugano

criteria at the end of induction (EOI) after 8 cycles of ATE, OBI and

VEN.

Results: R/R FL exhibited a higher amount of CD3

T‐cells, CD4

T‐

cells and CTL than R/R DLBCL (p<0.001, p=0.03 and p<0.001).

By contrast, R/R DLBCL contained more CD163

macrophages than

R/R FL (p=0.029). TIM3 expression was higher in R/R DLBLC vs R/R FL

(p=0.036), whereas PD1 expression was higher in R/R FL than R/R

DLCDL (p=0.008). ICP expression and ME composition did not

signiﬁcantly vary between GC and non‐CG DLBCL subtypes. As

compared to the initial diagnosis, expressions of TIM3 in FL and TIGIT

in DLBCL had a tendency to be increased at relapse, but no difference

in terms of immune cell composition was observed. PD1/PDL1

expression was not correlated with clinical response, whereas higher

expression of TIM3 and TIGIT (>15%) was associated with better

response in R/R FL (50% versus 33% of CR) and R/R DLBCL (40%

versus 0% of CR), respectively.

Conclusions: We show herein that TME composition and ICP

expression are distinct between R/R FL and R/R DLBCL and remain

mostly unchanged after R‐chemotherapy compared to initial biopsies,

except for higher TIM3 and TIGIT expression levels. This preliminary

study indicates that high expression of TIGIT in R/R DLBCL and TIM3 in

R/R FL patients are correlated with responsiveness following OBI‐

VEN‐ATE therapy. Thus, TIGIT and TIM3 expression could predict

the efﬁcacy of PD1/PD‐L1 blockade in these settings. Overall, these

data may reﬂect the triggering of a global T‐cell exhaustion program in

R/R B‐NHLs, which can be at least in part circumvented by anti‐PDL1

therapy. In future trials, targeting TIM3 and TIGIT might be considered

as a synergistic strategy to enhance the beneﬁt of PD1/PDL1 blockade

in these patients.

Keywords: Diagnostic and Prognostic Biomarkers

No conﬂicts of interests pertinent to the abstract.

298 |MICROENVIRONMENT IMMUNE CELLS IN BONE

MARROW AND LYMPH NODE MEASURED BY FLOW

CYTOMETRY CAN PREDICT SURVIVAL IN DIFFUSE LARGE B CELL

LYMPHOMA

L. Korin

, S. Cranco

, M. L. Fuente

, P. Ochoa

, A. Vitriu

, E. Babuin

F. Diaz Couselo

, A. Novoa

, P. Tempra

, M. B. Venegas

, A. Vijnovich

Baron

, N. Tartas

, M. R. Custidiano

, M. C. Foncuberta

, J. C.

Sanchez Avalos

Instituto Alexander Fleming, Hematology, Buenos Aires, Argentina,

Instituto Alexander Fleming, Internal Medicine, Buenos Aires, Argentina,

Instituto Alexander Fleming, Flow Cytometry, Buenos Aires, Argentina,

Cepacit, Pathology, Buenos Aires, Argentina

Introduction: Tumor microenvironment (TME) in diffuse large B‐cell

lymphoma (DLBCL) has recently been in the spotlight. The predictive

role of immune cells (IC) in peripheral blood (PB), bone marrow (BM)

and lymph nodes (LN) has been individually assessed, often using

techniques not widely available. However, data regarding the relative

prognostic impact of TME in each compartment evaluated simulta-

neously in DLBCL is still lacking.

SUPPLEMENT ABSTRACTS

393

Aims: To determine the prognostic impact on survival of the

Monocyte‐Lymphocyte prognostic score (MLS) in PB and the per-

centage (%) of IC in the BM and LN measured by ﬂow cytometry (FC)

in DLBCL.

Methods: We retrospectively collected information of patients (pts)

with DLBCL and available BM aspiration and LN FC data at diagnosis,

treated at our center between 2012 and 2019. Pts were stratiﬁed

according to the MLS (Wilcox et al, leukemia 2011) in two groups:

low (PB monocyte counts <630/ml and lymphocyte counts ≥1000/

ml) and intermediate‐high. FC analysis was performed with 8‐color

panels according to Euroﬂow protocols. % of BM and LN IC by FC

were compared to normal values determined by Matarraz (Cytom-

etry part B 2010) and Battaglia et al (Immunology 2003), and

analyzed in 3 categories: low, normal and high. Survival analysis was

performed with Kaplan‐meier (variables compared with log‐rank) and

Cox regression.

Results: 71 pts were included with a median age of 59 years. 49.3%

had poor R‐IPI. All pts received immunochemotherapy. Complete

remission rate was 82%. Median overall survival (OS) was 120.5

months (m), with a median follow up time of 34.7 m.

On univariate analysis TME variables from all the compartments

showed prognostic impact on OS. BM IC levels did not statistically

differ in involved vs not involved BM.

Both low LN TL % and high and low BM Mo % remained in-

dependent predictors of survival on multivariate analysis. Moreover,

pts with both of these unfavorable variables had a HR for death of

40.22 (CI 95% 5.16‐313.04, p <0.001) with a median OS of only

22.19 m.

Variables

Univariate

analysis Multivariate analysis

HR (95%

CI)

P‐

value

(95% CI) P‐value

LN T lymphocytes

(TL) low

3.98

(1.31‐

12.06)

0.014 5.44 (1.48‐

20.04)

0.011

BM B lymphocytes

low

4.73

(1.62‐

13.79)

0.004 3.36 (0.99‐

11,34)

0.0501

BM Monocytes (Mo)

High

10.53

(3.66‐

30.26)

<0.001 4.66 (1.34‐

16.25)

0.015

BM Monocytes Low 3.87

(1.28‐

11.7)

0.016 3.40 (1.05‐

10.99)

0.04

PB MLS

intermediate‐high

2.59

(1.12‐

0.02 1.05 (0.4‐

2.77)

0.91

Conclusion: Abnormal BM Mo % and low LN TL % measured by FC

were associated with inferior OS in our cohort of DLBCL pts. These

two TME variables presented at diagnosis could be easily translated

FIGURE 1 Kaplan‐meler estimates of

overall survival stratiﬁed by number of adverse

prognosis tumor microenviroment varaibles

present(low lymph node T‐lymphocytes and high

low bone marrow monocytes)

394

SUPPLEMENT ABSTRACTS

into prognostic biomarkers in DLBCL, identifying a subgroup of pts

with a dismal short term prognosis. In the future, therapies that

target the crosstalk between lymphoma cells and the LN and BM ME

might represent an encouraging strategy to improve outcomes in this

high risk subset of pts.

Keywords: Diagnostic and Prognostic Biomarkers

No conﬂicts of interests pertinent to the abstract.

299 |TARGETING DLBCL‐DERIVED EXOSOMES PREVENTS NK

CELL EXHAUSTION AND ELICITS POTENT ANTI‐TUMOR

IMMUNITY

F. Lu

, Y. Pang

, Y. Zhao

, J. Ye

, C. Ji

Qilu Hospital of Shandong University, Department of Hematology, Jinan,

China

SUPPLEMENT ABSTRACTS

395